ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.4002+1G>T

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, University of Leipzig Medical Center RCV001253084 SCV001428610 pathogenic Severe myoclonic epilepsy in infancy 2017-04-28 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV001507579 SCV001713204 likely pathogenic not provided 2020-10-09 criteria provided, single submitter clinical testing PVS1, PM2
LifeCell International Pvt. Ltd RCV001528184 SCV001739365 pathogenic Generalized epilepsy with febrile seizures plus, type 2 criteria provided, single submitter clinical testing A heterozygous 5’ splice site variation in intron 23 of the SCN1A gene (c.4002+1G>T) that affects the invariant GT donor splice-site of exon 23 was detected. The observed variant is not present in both the 1000 Genomes and gnomAD databases. The reference base is conserved across the species and in-silico predictions by Mutation taster, GeneSplicer, MaxEntScan, NNSplice are damaging. This variant has previously been reported for Epileptic encephalopathy by Mahdieh N et al., 2018. The gene has a low rate of benign loss of function variants as indicated by a high LoF variants Z-Score of 7.90. The variant is a loss of function variant in the gene, which is intolerant of Loss of Function variants, as indicated by the presence of existing pathogenic loss of function variant NP_001159435.1:p.M1I and 348 others. There are 338 downstream pathogenic loss of function variants, with the furthest variant being 591 residues downstream of the variant. Based on the above evidence this variant has been classified as pathogenic according to the ACMG guidelines.

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