ClinVar Miner

Submissions for variant NM_006922.4(SCN3A):c.1070G>A (p.Arg357Gln)

gnomAD frequency: 0.00005  dbSNP: rs774195502
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000819557 SCV000960223 uncertain significance not provided 2025-01-13 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 357 of the SCN3A protein (p.Arg357Gln). This variant is present in population databases (rs774195502, gnomAD 0.009%). This missense change has been observed in individual(s) with clinical features of SCN3A-related conditions (PMID: 24157691). ClinVar contains an entry for this variant (Variation ID: 522563). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt SCN3A protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects SCN3A function (PMID: 24157691). 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.
Revvity Omics, Revvity RCV000819557 SCV003823180 uncertain significance not provided 2019-09-19 criteria provided, single submitter clinical testing
GeneDx RCV000819557 SCV004167906 uncertain significance not provided 2023-10-09 criteria provided, single submitter clinical testing Reported previously in a single individual with focal epilepsy but no segregation information was available. Aside from SCN1A testing, no additional testing to rule out other possible causes of epilepsy was reported (Vanoye et al., 2014); Published functional studies demonstrate that the R357Q variant affects protein function consistent with hyper-excitability (Vanoye et al., 2014); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28488083, 31589614, 33236643, 29466837, 24157691)
OMIM RCV000625708 SCV000746208 pathogenic Epilepsy, familial focal, with variable foci 4 2020-09-01 no assertion criteria provided literature only

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