ClinVar Miner

Submissions for variant NM_000334.4(SCN4A):c.4547T>C (p.Met1516Thr)

gnomAD frequency: 0.00002  dbSNP: rs369886445
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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 RCV001067007 SCV001232035 uncertain significance Hyperkalemic periodic paralysis 2024-06-03 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1516 of the SCN4A protein (p.Met1516Thr). This variant is present in population databases (rs369886445, gnomAD 0.008%). 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: 860661). 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. 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 RCV002489700 SCV002775073 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 2021-12-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV002554506 SCV003526670 uncertain significance Inborn genetic diseases 2024-02-05 criteria provided, single submitter clinical testing The c.4547T>C (p.M1516T) alteration is located in exon 24 (coding exon 24) of the SCN4A gene. This alteration results from a T to C substitution at nucleotide position 4547, causing the methionine (M) at amino acid position 1516 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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