ClinVar Miner

Submissions for variant NM_000334.4(SCN4A):c.4705G>A (p.Gly1569Ser)

gnomAD frequency: 0.00003  dbSNP: rs774821803
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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 RCV000806452 SCV000946453 uncertain significance Hyperkalemic periodic paralysis 2024-11-27 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1569 of the SCN4A protein (p.Gly1569Ser). This variant is present in population databases (rs774821803, gnomAD 0.007%). This missense change has been observed in individual(s) with clinical features of SCN4A-related conditions (internal data). ClinVar contains an entry for this variant (Variation ID: 651154). 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 expected to disrupt SCN4A protein function with a positive predictive value of 95%. 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.
Fulgent Genetics, Fulgent Genetics RCV002477855 SCV002793648 uncertain significance Hypokalemic periodic paralysis, type 1; Potassium-aggravated myotonia; Paramyotonia congenita of Von Eulenburg; Hypokalemic periodic paralysis, type 2; Hyperkalemic periodic paralysis; Congenital myasthenic syndrome 16 2021-12-09 criteria provided, single submitter clinical testing
GeneDx RCV004777880 SCV005391752 uncertain significance not provided 2024-03-20 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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