ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.134A>G (p.Asp45Gly)

dbSNP: rs1559284606
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000729035 SCV000856669 uncertain significance not provided 2017-09-19 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001058607 SCV001223191 uncertain significance Early infantile epileptic encephalopathy with suppression bursts 2019-04-30 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals with SCN1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 593872). This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with glycine at codon 45 of the SCN1A protein (p.Asp45Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. 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: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C35"). 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. This variant disrupts the p.Asp45 amino acid residue in SCN1A. Other variant(s) that disrupt this residue have been observed in individuals with SCN1A-related conditions (PMID:23708187, 21248271, 29314583), which suggests that this may be a clinically significant amino acid residue.
GeneDx RCV000729035 SCV001999250 uncertain significance not provided 2019-08-27 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); The majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This substitution is predicted to be within the N-terminal cytoplasmic domain; Has not been previously published as pathogenic or benign to our knowledge

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