ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.4003G>A (p.Val1335Met)

dbSNP: rs121917960
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Bioinformatics, Peking University RCV000059408 SCV000221868 pathogenic Severe myoclonic epilepsy in infancy 2014-12-20 criteria provided, single submitter research
Labcorp Genetics (formerly Invitae), Labcorp RCV001202491 SCV001373604 pathogenic Early infantile epileptic encephalopathy with suppression bursts 2024-01-03 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1335 of the SCN1A protein (p.Val1335Met). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Dravet syndrome (PMID: 18413471, 18554359; Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 68535). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV003352765 SCV004077300 uncertain significance Inborn genetic diseases 2023-07-21 criteria provided, single submitter clinical testing The c.4003G>A (p.V1335M) alteration is located in exon 21 (coding exon 21) of the SCN1A gene. This alteration results from a G to A substitution at nucleotide position 4003, causing the valine (V) at amino acid position 1335 to be replaced by a methionine (M). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant has been reported in individuals with features consistent with Dravet syndrome, including one de novo occurrence (Sun, 2008; Zucca, 2008; Silvennoinen, 2021). This amino acid position is highly conserved in available vertebrate species. This alteration is predicted to be deleterious by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
UniProtKB/Swiss-Prot RCV000059408 SCV000090932 not provided Severe myoclonic epilepsy in infancy no assertion provided not provided

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