ClinVar Miner

Submissions for variant NM_000334.4(SCN4A):c.1808C>G (p.Thr603Arg)

gnomAD frequency: 0.00004  dbSNP: rs767603831
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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 RCV000801554 SCV000941334 uncertain significance Hyperkalemic periodic paralysis 2025-01-15 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with arginine, which is basic and polar, at codon 603 of the SCN4A protein (p.Thr603Arg). This variant is present in population databases (rs767603831, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with SCN4A-related conditions. ClinVar contains an entry for this variant (Variation ID: 647124). 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) has been performed 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. 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 RCV002495073 SCV002775687 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 2022-04-13 criteria provided, single submitter clinical testing
Ambry Genetics RCV004028067 SCV004944254 uncertain significance Inborn genetic diseases 2024-02-14 criteria provided, single submitter clinical testing The c.1808C>G (p.T603R) alteration is located in exon 11 (coding exon 11) of the SCN4A gene. This alteration results from a C to G substitution at nucleotide position 1808, causing the threonine (T) at amino acid position 603 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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