ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.1046A>C (p.Glu349Ala)

dbSNP: rs1574566659
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000804853 SCV000944789 uncertain significance Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 2022-07-05 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 349 of the SCN2A protein (p.Glu349Ala). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SCN2A-related conditions. ClinVar contains an entry for this variant (Variation ID: 649829). 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.
Ambry Genetics RCV004962821 SCV005500041 uncertain significance Inborn genetic diseases 2024-08-21 criteria provided, single submitter clinical testing The c.1046A>C (p.E349A) alteration is located in exon 9 (coding exon 8) of the SCN2A gene. This alteration results from an A to C substitution at nucleotide position 1046, causing the glutamic acid (E) at amino acid position 349 to be replaced by an alanine (A). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). 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.

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