[{"Approach":"Knockdown","Assessment text":"The variant NM_001040142.2:c.5636T>C (p.Met1879Thr) in SCN2A gene is classified as LP for Autosomal dominant SCN2A-related disorder. This variant is located in exon 27. The mechanism by which this variant impairs protein function is gain-of-function [PMID: 32750235]. There is published evidence [PMID:34850743,40263630] that ASO/RNAi/siRNA has already been developed and shown to work with available functional evidence. In light of the current evidence and in accordance with the consensus guidelines for assessing eligibility of pathogenic DNA variants for antisense oligonucleotide treatments, this variant is considered Eligible for knockdown ASO therapy.\nThis variant was assessed with v1.0 of the N1C VARIANT guidelines.","ClinVar":"https://www.ncbi.nlm.nih.gov/clinvar/variation/1478168/","Coding DNA change (c.)":"c.5636T>C","Confirmed protein or RNA change":"","Date assessment":"Sat, 15 Nov 2025 00:00:00 GMT","Eligibility":"Eligible","Gene":"SCN2A","Genomic sequence (g.)":"","ID":1,"Inheritance":"autosomal dominant","Pathomechanism":"gain-of-function","Predicted protein change (p.)":"p.Met1879Thr","Publication":"https://pubmed.ncbi.nlm.nih.gov/40263630/","RefSeq Transcript":"NM_001040142.2","Splicing effect?":"unknown","Therapeutic Modality":"Antisense Oligonucleotide","Unnamed: 18":"","Variant publication":""},{"Approach":"Splice Correction","Assessment text":"The variant NM_001130987.2(DYSF):c.1276+5G>A in DYSF gene is classified as LP/P for autosomal recessive dysferlinopathies which includes a spectrum of muscle disease. This variant is located in intron 12, 5 bp from donor splice site of the DYSF gene. There is published evidence [PMID:36983702] of the impact of this variant on splicing that leads to weakening of the canonical splice sites. In light of the current evidence and in accordance with the consensus guidelines for assessing eligibility of pathogenic DNA variants for antisense oligonucleotide treatments, this variant is considered NOT eligible for splice correction ASO therapy. This variant was assessed on 07/09/2025 using version 1 of the ASO eligibility guidelines established by the N=1 Collaborative.","ClinVar":"https://www.ncbi.nlm.nih.gov/clinvar/RCV000726343/","Coding DNA change (c.)":"c.1276+5G>A","Confirmed protein or RNA change":"p.(Met394SerfsTer27)/p.(Val385TrpfsTer5)","Date assessment":"Wed, 09 Jul 2025 00:00:00 GMT","Eligibility":"Not eligible","Gene":"DYSF","Genomic sequence (g.)":"","ID":2,"Inheritance":"autosomal recessive","Pathomechanism":"loss-of-function","Predicted protein change (p.)":"p. ?","Publication":"","RefSeq Transcript":"NM_001130987.2","Splicing effect?":"yes","Therapeutic Modality":"Antisense Oligonucleotide","Unnamed: 18":"","Variant publication":""},{"Approach":"Exon skipping","Assessment text":"The variant NM_001130987.2(DYSF):c.237-159_342+1237del is classified as P for autosomal recessive dysferlinopathies, which includes a spectrum of muscle disease. It is an intragenic deletion with intronic breakends that encompasses 4 of the DYSF gene(p.Phe80ProfsTer36) [PMID:36983702]. Exon 4 is out of- frame. Skipping exon 3 (adjacent out-of-frame) can potentially restore the reading frame. Skipping exon 3 along with the deleted exon 4 will result in the loss of 9.5% of protein length, including a part of the C2-1 (C2A) domain. The C2A domain is a functionally proven important domain which is crucial for dysferlin to function correctly in plasma membrane repair [PMID: 351567061]. In light of the current evidence and in accordance with the consensus guidelines for assessing eligibility of pathogenic DNA variants for antisense oligonucleotide treatments, this variant is considered NOT eligible for exon skipping ASO therapy. This variant was assessed on 09/03/2025 using version 1 of the ASO eligibility guidelines established by the N=1 Collaborative.","ClinVar":"https://www.ncbi.nlm.nih.gov/clinvar/variation/4056140/","Coding DNA change (c.)":"c.237-159_342+1237del  (exon 4 del)","Confirmed protein or RNA change":"p.(Phe80ProfsTer36)","Date assessment":"Wed, 03 Sep 2025 00:00:00 GMT","Eligibility":"Not eligible","Gene":"DYSF","Genomic sequence (g.)":"","ID":3,"Inheritance":"autosomal recessive","Pathomechanism":"loss-of-function","Predicted protein change (p.)":"p.?","Publication":"","RefSeq Transcript":"NM_001130987.2","Splicing effect?":"no","Therapeutic Modality":"Antisense Oligonucleotide","Unnamed: 18":"","Variant publication":"https://pubmed.ncbi.nlm.nih.gov/36983702/"},{"Approach":"Knockdown","Assessment text":"The variant NM_001330260.2(SCN8A):c.5615G>A (p.Arg1872Gln) in SCN8A gene is classified as P for SCN8A-related Epilepsy and/or Neurodevelopmental Disorders. There is published evidence [PMID: 26900580] that the variant causes a gain-of-function effect on protein function. There is published evidence [PMID:31943325,34412058,38113311] that an ASO/RNAi/siRNA has already been developed and shown to work with available functional evidence. In light of the current evidence and in accordance with the consensus guidelines for assessing eligibility of pathogenic DNA variants for antisense oligonucleotide treatments, this variant is considered eligible for RNA knockdown. This variant was assessed on 08/20/2025 using version 1 of the ASO eligibility guidelines established by the N=1 Collaborative\n","ClinVar":"https://www.ncbi.nlm.nih.gov/clinvar/RCV003992248.3/","Coding DNA change (c.)":"c.5615G>A","Confirmed protein or RNA change":"","Date assessment":"Wed, 20 Aug 2025 00:00:00 GMT","Eligibility":"Eligible ","Gene":"SCN8A","Genomic sequence (g.)":"","ID":4,"Inheritance":"autosomal dominant","Pathomechanism":"gain-of-function","Predicted protein change (p.)":"p.Arg1872Gln","Publication":"https://pubmed.ncbi.nlm.nih.gov/31943325/","RefSeq Transcript":"NM_001330260.2","Splicing effect?":"unknown","Therapeutic Modality":"Antisense Oligonucleotide","Unnamed: 18":"","Variant publication":"https://pubmed.ncbi.nlm.nih.gov/26900580/"},{"Approach":"","Assessment text":"The variant NM_001040142.2:(SCN2A):c.4780T>A (p.Trp1594Arg) in SCN2A is classified as LP for Autosomal dominant SCN2A-related disorder. This variant is located in exon 26.  There is no published evidence, at present, to determine the pathomechanism of the variant on protein function.  In light of the current evidence and in accordance with the consensus guidelines for assessing eligibility of pathogenic DNA variants for antisense oligonucleotide treatments, it is not possible to assess this variant for ASO therapy. This variant was assessed on 06/13/2025 using version 1 of the ASO eligibility guidelines established by the N=1 Collaborative","ClinVar":"https://www.ncbi.nlm.nih.gov/clinvar/RCV005430853/","Coding DNA change (c.)":"c.4780T>A ","Confirmed protein or RNA change":"","Date assessment":"Fri, 13 Jun 2025 00:00:00 GMT","Eligibility":"Unable to assess","Gene":"SCN2A","Genomic sequence (g.)":"","ID":5,"Inheritance":"autosomal dominant","Pathomechanism":"unknown","Predicted protein change (p.)":"p.Trp1594Arg","Publication":"","RefSeq Transcript":"NM_001040142.2","Splicing effect?":"unknown","Therapeutic Modality":"Antisense Oligonucleotide","Unnamed: 18":"","Variant publication":""},{"Approach":"Exon skipping","Assessment text":"The variant NM_001040142.2:c.5317G>A (p.Ala1773Thr) in SCN2A gene is classified as P for autosomal dominant SCN2A-related disorder. This variant is located in exon 27 of the SCN2A and associated with a loss-of-function [PMID:32400968]. Exon 27 is the last coding exon and is out of-frame. In light of the current evidence and in accordance with the consensus guidelines for assessing eligibility of pathogenic DNA variants for antisense oligonucleotide treatments, this variant is considered NOT Eligible for exon skipping ASO therapy. This variant was assessed on 06/09/2025 using version 1 of the ASO eligibility guidelines established by the N=1 Collaborative.","ClinVar":"https://www.ncbi.nlm.nih.gov/clinvar/variation/207024/","Coding DNA change (c.)":"c.5317G>A ","Confirmed protein or RNA change":"","Date assessment":"Mon, 09 Jun 2025 00:00:00 GMT","Eligibility":"Not eligible","Gene":"SCN2A","Genomic sequence (g.)":"","ID":6,"Inheritance":"autosomal dominant","Pathomechanism":"loss-of-function","Predicted protein change (p.)":"p.Ala1773Thr","Publication":"","RefSeq Transcript":"NM_001040142.2","Splicing effect?":"unknown","Therapeutic Modality":"Antisense Oligonucleotide","Unnamed: 18":"","Variant publication":"https://pubmed.ncbi.nlm.nih.gov/32400968/"},{"Approach":"Exon skipping","Assessment text":"The variant NM_003494.4(DYSF):c.533del p.(Gly178Glufs*49) in DYSF gene is classified as P for autosomal recessive dysferlinopathies which includes a spectrum of muscle disease.  This variant is located in exon 6 of the DYSF transcript (NM_003494.4). Exon 6 is out of frame. In light of the current evidence and in accordance with the consensus guidelines for assessing eligibility of pathogenic DNA variants for antisense oligonucleotide treatments, this variant is considered NOT eligible for exon skipping ASO therapy. This variant was assessed on 09/03/2025 using version 1 of the ASO eligibility guidelines established by the N=1 Collaborative.","ClinVar":"https://www.ncbi.nlm.nih.gov/clinvar/RCV005600403/","Coding DNA change (c.)":"c.533del","Confirmed protein or RNA change":"","Date assessment":"Wed, 03 Sep 2025 00:00:00 GMT","Eligibility":"Not eligible","Gene":"DYSF","Genomic sequence (g.)":"","ID":7,"Inheritance":"autosomal dominant","Pathomechanism":"","Predicted protein change (p.)":"p.Gly178Glufs*49","Publication":"","RefSeq Transcript":"NM_003494.4","Splicing effect?":"unknown","Therapeutic Modality":"Antisense Oligonucleotide","Unnamed: 18":"","Variant publication":""},{"Approach":"","Assessment text":"The variant NM_001165963.4(SCN1A):c.2792G>A (p.Arg931His) in SCN1A gene is classified as pathogenic for autosomal dominant SCN1A-related disorder. This variant is located in exon 18.  There is no published evidence, at present, to determine the pathomechanism of the variant on protein function. In light of the current evidence and in accordance with the consensus guidelines for assessing eligibility of pathogenic DNA variants for antisense oligonucleotide treatments, it is not possible to assess this variant for ASO therapy. This variant was assessed on 08/06/2025 using version 1 of the ASO eligibility guidelines established by the N=1 Collaborative.","ClinVar":"https://www.ncbi.nlm.nih.gov/clinvar/variation/189869/","Coding DNA change (c.)":"c.2792G>A","Confirmed protein or RNA change":"","Date assessment":"Wed, 06 Aug 2025 00:00:00 GMT","Eligibility":"Unable to assess","Gene":"SCN1A","Genomic sequence (g.)":"","ID":8,"Inheritance":"autosomal dominant","Pathomechanism":"unknown","Predicted protein change (p.)":"p.Arg931His","Publication":"","RefSeq Transcript":"NM_001165963.4","Splicing effect?":"unknown","Therapeutic Modality":"Antisense Oligonucleotide","Unnamed: 18":"","Variant publication":""},{"Approach":"","Assessment text":"The variant NM_001165963.4(SCN1A):c.1709G>A (p.Ser570Asn) in SCN1A gene is classified as likely pathogenic for autosomal dominant SCN1A-related disorder. This variant is located in exon 14.  There is no published evidence, at present, to determine the pathomechanism of the variant on protein function. In light of the current evidence and in accordance with the consensus guidelines for assessing eligibility of pathogenic DNA variants for antisense oligonucleotide treatments, it is not possible to assess this variant for ASO therapy. This variant was assessed on 08/06/2025 using version 1 of the ASO eligibility guidelines established by the N=1 Collaborative.","ClinVar":"https://www.ncbi.nlm.nih.gov/clinvar/variation/374331/","Coding DNA change (c.)":"c.1709G>A","Confirmed protein or RNA change":"","Date assessment":"Wed, 06 Aug 2025 00:00:00 GMT","Eligibility":"Unable to assess","Gene":"SCN1A","Genomic sequence (g.)":"","ID":9,"Inheritance":"autosomal dominant","Pathomechanism":"unknown","Predicted protein change (p.)":"p.Ser570Asn","Publication":"","RefSeq Transcript":"NM_001165963.4","Splicing effect?":"unknown","Therapeutic Modality":"Antisense Oligonucleotide","Unnamed: 18":"","Variant publication":""},{"Approach":"","Assessment text":"The variant NM_001165963.4(SCN1A):c.3629C>T (p.Thr1210Met) in SCN1A gene is classified as likely pathogenic for autosomal dominant SCN1A-related disorder. This variant is located in exon 21.  There is no published evidence, at present, to determine the pathomechanism of the variant on protein function. In light of the current evidence and in accordance with the consensus guidelines for assessing eligibility of pathogenic DNA variants for antisense oligonucleotide treatments, it is not possible to assess this variant for ASO therapy. This variant was assessed on 08/06/2025 using version 1 of the ASO eligibility guidelines established by the N=1 Collaborative.","ClinVar":"https://www.ncbi.nlm.nih.gov/clinvar/variation/658067/","Coding DNA change (c.)":"c.3629C>T","Confirmed protein or RNA change":"","Date assessment":"Wed, 06 Aug 2025 00:00:00 GMT","Eligibility":"Unable to assess","Gene":"SCN1A","Genomic sequence (g.)":"","ID":10,"Inheritance":"autosomal dominant","Pathomechanism":"unknown","Predicted protein change (p.)":"p.Thr1210Met","Publication":"","RefSeq Transcript":"NM_001165963.4","Splicing effect?":"unknown","Therapeutic Modality":"Antisense Oligonucleotide","Unnamed: 18":"","Variant publication":""},{"Approach":"","Assessment text":"The variant NM_001165963.4(SCN1A):c.4916G>C (p.Arg1639Pro) in SCN1A gene is classified as pathogenic for autosomal dominant SCN1A-related disorder. This variant is located in exon 29.  There is no published evidence, at present, to determine the pathomechanism of the variant on protein function. In light of the current evidence and in accordance with the consensus guidelines for assessing eligibility of pathogenic DNA variants for antisense oligonucleotide treatments, it is not possible to assess this variant for ASO therapy. This variant was assessed on 07/04/2025 using version 1 of the ASO eligibility guidelines established by the N=1 Collaborative.","ClinVar":"https://www.ncbi.nlm.nih.gov/clinvar/variation/206852/","Coding DNA change (c.)":"c.4916G>C","Confirmed protein or RNA change":"","Date assessment":"Fri, 04 Jul 2025 00:00:00 GMT","Eligibility":"Unable to assess","Gene":"SCN1A","Genomic sequence (g.)":"","ID":11,"Inheritance":"autosomal dominant","Pathomechanism":"unknown","Predicted protein change (p.)":"p.Arg1639Pro","Publication":"","RefSeq Transcript":"NM_001165963.4","Splicing effect?":"unknown","Therapeutic Modality":"Antisense Oligonucleotide","Unnamed: 18":"","Variant publication":""},{"Approach":"Exon skipping","Assessment text":"The variant NM_001130987.2(DYSF):c.4873C>T (p.Arg1625Ter) in DYSF gene is classified as pathogenic for autosomal recessive dysferlinopathies which includes a spectrum of muscle disease. This variant is located in exon 44 of the DYSF gene. Exon 44 is in-frame AND codes for \u22645% of the protein. Exon skipping does not create a stop codon, but exon 44 includes a part of the sixth C2 domain (C2F domain). In light of the current evidence and in accordance with the consensus guidelines for assessing eligibility of pathogenic DNA variants for antisense oligonucleotide treatments, this variant is considered unlikely eligible for exon skipping ASO therapy. This variant was assessed on 07/15/2025 using version 1 of the ASO eligibility guidelines established by the N=1 Collaborative.","ClinVar":"https://www.ncbi.nlm.nih.gov/clinvar/variation/94330/","Coding DNA change (c.)":"c.4873C>T","Confirmed protein or RNA change":"","Date assessment":"Tue, 15 Jul 2025 00:00:00 GMT","Eligibility":"Unlikely eligible","Gene":"DYSF","Genomic sequence (g.)":"","ID":12,"Inheritance":"autosomal recessive","Pathomechanism":"loss-of-function","Predicted protein change (p.)":"p.Arg1625Ter","Publication":"","RefSeq Transcript":"NM_001130987.2","Splicing effect?":"unknown","Therapeutic Modality":"Antisense Oligonucleotide","Unnamed: 18":"","Variant publication":""},{"Approach":"Knockdown","Assessment text":"The variant NM_021007.3(SCN2A):c.2558G>A p.(p.Arg853Gln) in SCN2A gene is classified as pathogenic for autosomal dominant SCN2A-related disorder). The mechanism by which this variant impairs protein function is loss-of-function [PMID:35637276,34287911], although mixed gain/loss of function variant has been suggested (https://aesnet.org/abstractslisting/individualized-antisense-oligonucleotide-for-two-patients-with-developmental-epileptic-encephalopathy-due-to-nano-rare-causal-scn2a-variants-same-gene-different-treatment). A knockdown ASO therapy has been developed for an individual carrying this variant which has already been delivered clinically.Therefore, this variant is considered eligible for a knockdown approach.  This variant was assessed on 11/15/2025 using version 1 of the ASO eligibility guidelines established by the N=1 Collaborative.","ClinVar":"https://www.ncbi.nlm.nih.gov/clinvar/variation/194555/","Coding DNA change (c.)":"c.2558G>A","Confirmed protein or RNA change":"","Date assessment":"Sat, 15 Nov 2025 00:00:00 GMT","Eligibility":"Eligible ","Gene":"SCN2A","Genomic sequence (g.)":"","ID":15,"Inheritance":"autosomal dominant","Pathomechanism":"mixed gain-/loss-of-function","Predicted protein change (p.)":"p.Arg853Gln","Publication":"","RefSeq Transcript":"NM_021007.3","Splicing effect?":"unknown","Therapeutic Modality":"Antisense Oligonucleotide","Unnamed: 18":"Note to team: please review evidence of pathogenicity, in relation to N-lorem poster, also therapy is under development, it seems to be knockdown from the clinical trial entry","Variant publication":""},{"Approach":"Exon skipping","Assessment text":"The variant NM_000070.3(CAPN3):c.2105C>T (p.Ala702Val) in CAPN3 gene is classified as pathogenic for CAPN3-related autosomal recessive limb-girdle muscular dystrophy (Calpainopathy). This variant is located in exon 19 of CAPN3. Exon19 is out of-frame. In light of the current evidence and in accordance with the consensus guidelines for assessing eligibility of pathogenic DNA variants for antisense oligonucleotide treatments, this variant is considered NOT eligible for exon skipping ASO therapy. This variant was assessed on 07/15/2025 using version 1 of the ASO eligibility guidelines established by the N=1 Collaborative.","ClinVar":"https://www.ncbi.nlm.nih.gov/clinvar/variation/283099/","Coding DNA change (c.)":"c.2105C>T","Confirmed protein or RNA change":"","Date assessment":"Tue, 15 Jul 2025 00:00:00 GMT","Eligibility":"Not eligible","Gene":"CAPN3","Genomic sequence (g.)":"","ID":16,"Inheritance":"autosomal recessive","Pathomechanism":"","Predicted protein change (p.)":"p.Ala702Val","Publication":"","RefSeq Transcript":"NM_000070.3","Splicing effect?":"unknown","Therapeutic Modality":"Antisense Oligonucleotide","Unnamed: 18":"","Variant publication":""},{"Approach":"","Assessment text":"The variant NM_001165963.4(SCN1A):c.4465C>A (p.Gln1489Lys) in SCN1A gene is classified as pathogenic for autosomal dominant SCN1A-related disorder. This variant is located in exon 26.  The published evidence suggest that the variant pathomechanism is mixed gain-of-function/loss-of-function [PMID:18621678,18632931]. Given the ambiguous pathomechanism it is unclear whether a knockdown or upregulation approach will be necessary in this case. This variant is located in exon 26. Exon 26 is an in-frame exon AND codes for \u22645% of the protein. Exon skipping does not create a stop codon but exon 26 includes part of the cytoplasmic linker between domains III and IV, which is critical for fast inactivation. This variant resides within a Pathogenic Enriched Region that is defined as a mutational hotspot by the ClinGen Epilepsy Sodium Channel VCEP. Skipping this variant will lead to a loss of function and cannot be recommended if restoration of function would be necessary for this variant. This variant was assessed on 07/04/2025 using version 1 of the ASO eligibility guidelines established by the N=1 Collaborative.","ClinVar":"https://www.ncbi.nlm.nih.gov/clinvar/variation/12893/","Coding DNA change (c.)":"c.4465C>A","Confirmed protein or RNA change":"","Date assessment":"Fri, 04 Jul 2025 00:00:00 GMT","Eligibility":"Unable to assess","Gene":"SCN1A","Genomic sequence (g.)":"","ID":17,"Inheritance":"autosomal recessive","Pathomechanism":"mixed gain-/loss-of-function ","Predicted protein change (p.)":"p.Gln1489Lys","Publication":"","RefSeq Transcript":"NM_001165963.4","Splicing effect?":"unknown","Therapeutic Modality":"Antisense Oligonucleotide","Unnamed: 18":"","Variant publication":""},{"Approach":"Exon skipping","Assessment text":"The variant NM_001130987.2(DYSF):c.3167G>C (p.Arg1056Pro) in DYSF gene is classified as pathogenic for autosomal recessive dysferlinopathies which includes a spectrum of muscle disease. This variant is located in exon 29 of the DYSF gene. Exon 29 is out of-frame. In light of the current evidence and in accordance with the consensus guidelines for assessing eligibility of pathogenic DNA variants for antisense oligonucleotide treatments, this variant is considered NOT eligible for exon skipping ASO therapy. This variant was assessed on 08/06/2025 using version 1 of the ASO eligibility guidelines established by the N=1 Collaborative.","ClinVar":"https://www.ncbi.nlm.nih.gov/clinvar/variation/2912979","Coding DNA change (c.)":"c.3167G>C","Confirmed protein or RNA change":"","Date assessment":"Wed, 06 Aug 2025 00:00:00 GMT","Eligibility":"Not eligible ","Gene":"DYSF","Genomic sequence (g.)":"","ID":18,"Inheritance":"autosomal recessive","Pathomechanism":"","Predicted protein change (p.)":"p.Arg1056Pro","Publication":"","RefSeq Transcript":"NM_001130987.2","Splicing effect?":"unknown","Therapeutic Modality":"Antisense Oligonucleotide","Unnamed: 18":"","Variant publication":""},{"Approach":"Exon skipping","Assessment text":"The variant NM_001130987.2(DYSF):c.5815_5816del (p.Ser1939fs) in DYSF gene is classified as pathogenic for autosomal recessive dysferlinopathies which includes a spectrum of muscle disease. This variant is located in exon 51 of the DYSF gene. Exon 51 is out of-frame. In light of the current evidence and in accordance with the consensus guidelines for assessing eligibility of pathogenic DNA variants for antisense oligonucleotide treatments, this variant is considered NOT eligible for exon skipping ASO therapy. This variant was assessed on 08/06/2025 using version 1 of the ASO eligibility guidelines established by the N=1 Collaborative.","ClinVar":"https://www.ncbi.nlm.nih.gov/clinvar/variation/94344","Coding DNA change (c.)":"c.5815_5816del","Confirmed protein or RNA change":"","Date assessment":"Wed, 06 Aug 2025 00:00:00 GMT","Eligibility":"Not eligible ","Gene":"DYSF","Genomic sequence (g.)":"","ID":19,"Inheritance":"autosomal recessive","Pathomechanism":"","Predicted protein change (p.)":"p.Ser1939Glnfs*14","Publication":"","RefSeq Transcript":"NM_001130987.2","Splicing effect?":"unknown","Therapeutic Modality":"Antisense Oligonucleotide","Unnamed: 18":"","Variant publication":""},{"Approach":"Exon skipping","Assessment text":"The variant NM_001130987.2(DYSF):c.268C>T (p.Arg90Ter) in DYSF gene is classified as pathogenic for autosomal recessive dysferlinopathies which includes a spectrum of muscle disease. This variant is located in exon 4 of the DYSF gene. Exon 4 is out of-frame. In light of the current evidence and in accordance with the consensus guidelines for assessing eligibility of pathogenic DNA variants for antisense oligonucleotide treatments, this variant is considered NOT eligible for exon skipping ASO therapy. This variant was assessed on 07/15/2025 using version 1 of the ASO eligibility guidelines established by the N=1 Collaborative.","ClinVar":"https://www.ncbi.nlm.nih.gov/clinvar/variation/197217","Coding DNA change (c.)":"c.268C>T ","Confirmed protein or RNA change":"","Date assessment":"Tue, 15 Jul 2025 00:00:00 GMT","Eligibility":"Not eligible ","Gene":"DYSF","Genomic sequence (g.)":"","ID":20,"Inheritance":"autosomal recessive","Pathomechanism":"","Predicted protein change (p.)":"p.Arg90Ter","Publication":"","RefSeq Transcript":"NM_001130987.2","Splicing effect?":"unknown","Therapeutic Modality":"Antisense Oligonucleotide","Unnamed: 18":"","Variant publication":""},{"Approach":"Exon skipping","Assessment text":"The variant NM_001130987.2(DYSF):c.3859dup (p.Glu1287Glyfs*7) in DYSF gene is classified as pathogenic for autosomal recessive dysferlinopathies which includes a spectrum of muscle disease. This variant is located in exon 34 of the DYSF gene. Exon 34 is in-frame AND codes for \u22645% of the protein. Exon skipping does not create a stop codon but exon 34 includes a part of the fourth C2 domain (C2D domain). It has been suggested that exon 34 skipping might be pathogenic such as c.3843+2T>A, however, data has been obtained via midi-gene splicing assays and at thus not accounted for in the evaluation [PMID:25312915]. In light of the current evidence and in accordance with the consensus guidelines for assessing eligibility of pathogenic DNA variants for antisense oligonucleotide treatments, this variant is considered unlikely eligible for exon skipping ASO therapy. This variant was assessed on 08/01/2025 using version 1 of the ASO eligibility guidelines established by the N=1 Collaborative.","ClinVar":"https://www.ncbi.nlm.nih.gov/clinvar/variation/646166","Coding DNA change (c.)":"c.3859dup","Confirmed protein or RNA change":"","Date assessment":"Fri, 01 Aug 2025 00:00:00 GMT","Eligibility":"Unlikely eligible","Gene":"DYSF","Genomic sequence (g.)":"","ID":21,"Inheritance":"autosomal recessive","Pathomechanism":"","Predicted protein change (p.)":"p.Glu1287Glyfs*7","Publication":"","RefSeq Transcript":"NM_001130987.2","Splicing effect?":"unknown","Therapeutic Modality":"Antisense Oligonucleotide","Unnamed: 18":"","Variant publication":""},{"Approach":"","Assessment text":"The variant NM_001165963.4(SCN1A):c.2303C>T (p.Pro768Leu) in SCN1A gene is classified as likely pathogenic for autosomal dominant SCN1A-related disorder. This variant is located in exon 16.  There is no published evidence, at present, to determine the pathomechanism of the variant on protein function. In light of the current evidence and in accordance with the consensus guidelines for assessing eligibility of pathogenic DNA variants for antisense oligonucleotide treatments, it is not possible to assess this variant for ASO therapy. This variant was assessed on 06/17/2025 using version 1 of the ASO eligibility guidelines established by the N=1 Collaborative.","ClinVar":"https://www.ncbi.nlm.nih.gov/clinvar/variation/189929","Coding DNA change (c.)":"c.2303C>T","Confirmed protein or RNA change":"","Date assessment":"Tue, 17 Jun 2025 00:00:00 GMT","Eligibility":"Unable to assess","Gene":"SCN1A","Genomic sequence (g.)":"","ID":22,"Inheritance":"autosomal dominant","Pathomechanism":"unknown","Predicted protein change (p.)":"p.Pro768Leu","Publication":"","RefSeq Transcript":"NM_001165963.4","Splicing effect?":"unknown","Therapeutic Modality":"Antisense Oligonucleotide","Unnamed: 18":"","Variant publication":""},{"Approach":"","Assessment text":"The variant NM_021007.3(SCN2A):c.4782G>T p.(Trp1594Cys) in SCN2A is classified as likely pathogenic for autosomal dominant SCN2A-related disorder. This variant is located in exon 26.  There is no published evidence, at present, to determine the pathomechanism of the variant on protein function.  In light of the current evidence and in accordance with the consensus guidelines for assessing eligibility of pathogenic DNA variants for antisense oligonucleotide treatments, it is not possible to assess this variant for ASO therapy. This variant was assessed on 06/16/2025 using version 1 of the ASO eligibility guidelines established by the N=1 Collaborative.","ClinVar":"https://www.ncbi.nlm.nih.gov/clinvar/variation/3906896","Coding DNA change (c.)":"c.4782G>T","Confirmed protein or RNA change":"","Date assessment":"Mon, 16 Jun 2025 00:00:00 GMT","Eligibility":"Unable to assess","Gene":"SCN2A","Genomic sequence (g.)":"","ID":23,"Inheritance":"autosomal dominant","Pathomechanism":"unknown","Predicted protein change (p.)":"p.Trp1594Cys","Publication":"","RefSeq Transcript":"NM_021007.3","Splicing effect?":"unknown","Therapeutic Modality":"Antisense Oligonucleotide","Unnamed: 18":"","Variant publication":""},{"Approach":"","Assessment text":"The variant NM_001040142.2(SCN2A) c.2657T>C (p.Leu886Ser) in SCN2A is classified as likely pathogenic for autosomal dominant SCN2A-related disorder. This variant is located in exon 16. There is no published evidence, at present, to determine the pathomechanism of the variant on protein function.  In light of the current evidence and in accordance with the consensus guidelines for assessing eligibility of pathogenic DNA variants for antisense oligonucleotide treatments, it is not possible to assess this variant for ASO therapy. This variant was assessed on 06/18/2025 using version 1 of the ASO eligibility guidelines established by the N=1 Collaborative.","ClinVar":"https://www.ncbi.nlm.nih.gov/clinvar/variation/206972","Coding DNA change (c.)":"c.2657T>C","Confirmed protein or RNA change":"","Date assessment":"Wed, 18 Jun 2025 00:00:00 GMT","Eligibility":"Unable to assess","Gene":"SCN2A","Genomic sequence (g.)":"","ID":24,"Inheritance":"autosomal dominant","Pathomechanism":"unknown","Predicted protein change (p.)":"p.Leu886Ser","Publication":"","RefSeq Transcript":"NM_001040142.2","Splicing effect?":"unknown","Therapeutic Modality":"Antisense Oligonucleotide","Unnamed: 18":"","Variant publication":""},{"Approach":"","Assessment text":"The variant NM_001040142.2(SCN2A):c.1094C>T (p.Thr365Met) in SCN2A is classified as likely pathogenic for autosomal dominant SCN2A-related disorder. This variant is located in exon 9.  There is no published evidence, at present, to determine the pathomechanism of the variant on protein function.  In light of the current evidence and in accordance with the consensus guidelines for assessing eligibility of pathogenic DNA variants for antisense oligonucleotide treatments, it is not possible to assess this variant for ASO therapy. This variant was assessed on 06/09/2025 using version 1 of the ASO eligibility guidelines established by the N=1 Collaborative.","ClinVar":"https://www.ncbi.nlm.nih.gov/clinvar/variation/2435687/","Coding DNA change (c.)":"c.1094C>T","Confirmed protein or RNA change":"","Date assessment":"Mon, 09 Jun 2025 00:00:00 GMT","Eligibility":"Unable to assess","Gene":"SCN2A","Genomic sequence (g.)":"","ID":25,"Inheritance":"autosomal dominant","Pathomechanism":"unknown","Predicted protein change (p.)":"p.Thr365Met","Publication":"","RefSeq Transcript":"NM_001040142.2","Splicing effect?":"unknown","Therapeutic Modality":"Antisense Oligonucleotide","Unnamed: 18":"","Variant publication":""},{"Approach":"Exon skipping","Assessment text":"The variant NM_006922.4(SCN3A):c.585_586del (p.Phe195LeufsTer54) in SCN3A is classified as pathogenic for autosomal dominant SCN3A-related disorder. This variant is located in exon 6. Exon 6 is in-frame AND codes for \u22645% of the protein. Exon skipping does not create a stop codon but exon 6 includes a part of the cytoplasmic loop between repeats I and II, which is critical for channel function and is particularly important for modulation of channel gating and interacting with other proteins.  In light of the current evidence and in accordance with the consensus guidelines for assessing eligibility of pathogenic DNA variants for antisense oligonucleotide treatments, this variant is considered NOT eligible for exon skipping ASO therapy. There is no published evidence, at present, to determine the pathomechanism of the variant on protein function. Therefore, this assessment should be interpreted with caution as further studies are required to determine the pathomechanism of the variant on protein function. This variant was assessed on 07/15/2025 using version 1 of the ASO eligibility guidelines established by the N=1 Collaborative.","ClinVar":"https://www.ncbi.nlm.nih.gov/clinvar/variation/1365761","Coding DNA change (c.)":"c.585_586del","Confirmed protein or RNA change":"","Date assessment":"Tue, 15 Jul 2025 00:00:00 GMT","Eligibility":"Unlikely eligible","Gene":"SCN3A","Genomic sequence (g.)":"","ID":26,"Inheritance":"autosomal dominant","Pathomechanism":"unknown","Predicted protein change (p.)":"p.Phe195LeufsTer54","Publication":"","RefSeq Transcript":"NM_006922.4","Splicing effect?":"unknown","Therapeutic Modality":"Antisense Oligonucleotide","Unnamed: 18":"SCN3A has mutually exclusive alternative exons for exon 6, and a variant including exon 6N is expressed in the fetal brain, while another including exon 6A is present in the adult brain, not eligible vs unlikely eligible, depends on protein function ","Variant publication":""},{"Approach":"","Assessment text":"The variant NM_001330260.2(SCN8A):c.3953A>G (p.Asn1318Ser) in SCN8A is classified as P/LP for autosomal dominant SCN8A-related disorder. This variant is located in exon 22.  There is no published evidence, at present, to determine the pathomechanism of the variant on protein function.  In light of the current evidence and in accordance with the consensus guidelines for assessing eligibility of pathogenic DNA variants for antisense oligonucleotide treatments, it is not possible to assess this variant for ASO therapy. This variant was assessed on 06/09/2025 using version 1 of the ASO eligibility guidelines established by the N=1 Collaborative.","ClinVar":"https://www.ncbi.nlm.nih.gov/clinvar/variation/694309","Coding DNA change (c.)":"c.3953A>G","Confirmed protein or RNA change":"","Date assessment":"Mon, 09 Jun 2025 00:00:00 GMT","Eligibility":"Unable to assess","Gene":"SCN8A","Genomic sequence (g.)":"","ID":27,"Inheritance":"autosomal dominant","Pathomechanism":"unknown","Predicted protein change (p.)":"p.Asn1318Ser","Publication":"","RefSeq Transcript":"NM_001330260.2","Splicing effect?":"unknown","Therapeutic Modality":"Antisense Oligonucleotide","Unnamed: 18":"","Variant publication":""}]