ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.2990A>G (p.Asp997Gly)

dbSNP: rs1057523786
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000438096 SCV000533319 pathogenic not provided 2022-03-07 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This substitution is predicted to be in the cytoplasmic loop between the second and third homologous domains.; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001059949 SCV001224604 uncertain significance Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 2019-04-16 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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"). This variant has not been reported in the literature in individuals with SCN2A-related conditions. ClinVar contains an entry for this variant (Variation ID: 390480). This sequence change replaces aspartic acid with glycine at codon 997 of the SCN2A protein (p.Asp997Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine.
CeGaT Center for Human Genetics Tuebingen RCV000438096 SCV001502320 uncertain significance not provided 2020-12-01 criteria provided, single submitter clinical testing
Channelopathy-Associated Epilepsy Research Center RCV003483613 SCV004232401 not provided Complex neurodevelopmental disorder no assertion provided literature only

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