ClinVar Miner

Submissions for variant NM_006922.4(SCN3A):c.5947A>C (p.Lys1983Gln)

dbSNP: rs774354894
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Neuberg Centre For Genomic Medicine, NCGM RCV001823594 SCV002073158 uncertain significance Developmental and epileptic encephalopathy, 62 criteria provided, single submitter clinical testing The missense variant p.K1983Q in SCN3A (NM_006922.4) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The variant is observed in 4/29,646 (0.0135%) alleles from individuals of South Asian background in gnomAD Exomes. There is a small physicochemical difference between lysine and glutamine, which is not likely to impact secondary protein structure as these residues share similar properties. Insilico tools predict a damaging effect (SIFT). For these reasons, this variant has been classified as Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV002545195 SCV003463038 uncertain significance not provided 2022-06-22 criteria provided, single submitter clinical testing 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 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: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with SCN3A-related conditions. This variant is present in population databases (rs774354894, gnomAD 0.01%). This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1983 of the SCN3A protein (p.Lys1983Gln).
Neuberg Centre For Genomic Medicine, NCGM RCV003339757 SCV004047064 uncertain significance Epilepsy, familial focal, with variable foci 1 criteria provided, single submitter clinical testing The c.5947A>C (p.Lys1983Gln) missense variant in SCN3A gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is reported with the allele frequency (0.001%) in the gnomAD and novel in 1000 genome database. The amino acid Lys at position 1983 is changed to a Gln changing protein sequence and it might alter its composition and physico-chemical properties. In silico tools predict the variant to be tolerated. The residue is conserved across species. The amino acid change p.Lys1983Gln in SCN3A is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Variant of Uncertain Significance (VUS).

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