ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.2021C>A (p.Thr674Lys)

gnomAD frequency: 0.00001  dbSNP: rs1698384021
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001069713 SCV001234903 uncertain significance Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 2022-03-15 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 674 of the SCN2A protein (p.Thr674Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autism spectrum disorder (PMID: 26637798). This missense change has been observed in at least one individual who was not affected with SCN2A-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 862884). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
GeneDx RCV001796362 SCV002032578 uncertain significance not provided 2021-05-05 criteria provided, single submitter clinical testing Reported previously in an individual with autism, but additional clinical information was not provided (D'Gama et al., 2015); Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); 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 first and second homologous domains; This variant is associated with the following publications: (PMID: 26637798)
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre RCV003992437 SCV004809829 uncertain significance Episodic ataxia, type 9 2024-04-04 criteria provided, single submitter clinical testing

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