ClinVar Miner

Submissions for variant NM_000334.4(SCN4A):c.4897C>G (p.Gln1633Glu)

dbSNP: rs2144773878
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV001663807 SCV001879499 likely pathogenic not provided 2020-11-23 criteria provided, single submitter clinical testing This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). This variant has been identified in at least one individual with clinical features associated with this gene. Assessment of experimental evidence suggests this variant results in abnormal protein function. This variant causes a disruption of normal sodium channel function (PMID: 19347921). Computational tools predict that this variant is pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV003505180 SCV004297507 likely pathogenic Familial hyperkalemic periodic paralysis 2023-03-28 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this missense change affects SCN4A function (PMID: 19347921). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SCN4A protein function. ClinVar contains an entry for this variant (Variation ID: 1256465). This missense change has been observed in individuals with clinical feature of autosomal dominant SCN4A-related conditions (PMID: 19347921; Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 1633 of the SCN4A protein (p.Gln1633Glu).

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