ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.4687C>G (p.Leu1563Val)

dbSNP: rs121917750
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255820 SCV000322245 pathogenic not provided 2025-01-24 criteria provided, single submitter clinical testing Published functional studies demonstrate that L1563V causes a gain of channel function and increases neuronal excitability in neonatal sodium channels (PMID: 18479388, 17467289); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This substitution is predicted to be within the transmembrane segment S2 of the fourth homologous domain; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 15301839, 18537643, 22029951, 3508699, 17467289, 17021166, 28256214, 28717674, 32090326, 32291436, 34425903, 29691040, 35637276, 32845893, 31904120, 33769100, 29844171, 31995133, 30813884, 12243921, 18479388)
Labcorp Genetics (formerly Invitae), Labcorp RCV002513022 SCV003525057 pathogenic Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 2022-04-13 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 12877). This missense change has been observed in individual(s) with benign familial neonatal-infantile seizures (PMID: 12243921). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1563 of the SCN2A protein (p.Leu1563Val). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects SCN2A function (PMID: 17021166, 17467289, 18479388).
OMIM RCV000013737 SCV000033984 pathogenic Seizures, benign familial infantile, 3 2002-09-14 no assertion criteria provided literature only
Channelopathy-Associated Epilepsy Research Center RCV002319421 SCV002605508 not provided Complex neurodevelopmental disorder no assertion provided literature only

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