ClinVar Miner

Submissions for variant NM_000334.4(SCN4A):c.5179G>A (p.Glu1727Lys)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002579180 SCV003490437 uncertain significance Hyperkalemic periodic paralysis 2023-12-06 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1727 of the SCN4A protein (p.Glu1727Lys). This variant is present in population databases (rs747666894, gnomAD 0.006%). 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: 2175383). 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) performed at Invitae 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.
Ambry Genetics RCV004073432 SCV004943804 uncertain significance Inborn genetic diseases 2023-11-29 criteria provided, single submitter clinical testing The c.5179G>A (p.E1727K) alteration is located in exon 24 (coding exon 24) of the SCN4A gene. This alteration results from a G to A substitution at nucleotide position 5179, causing the glutamic acid (E) at amino acid position 1727 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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