ClinVar Miner

Submissions for variant NM_000334.4(SCN4A):c.1606G>A (p.Glu536Lys)

gnomAD frequency: 0.00003  dbSNP: rs746256985
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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 RCV001294875 SCV001483772 uncertain significance Hyperkalemic periodic paralysis 2022-08-16 criteria provided, single submitter clinical testing 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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 998946). This variant has not been reported in the literature in individuals affected with SCN4A-related conditions. This variant is present in population databases (rs746256985, gnomAD 0.01%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 536 of the SCN4A protein (p.Glu536Lys). This variant also falls at the last nucleotide of exon 10, which is part of the consensus splice site for this exon.
Fulgent Genetics, Fulgent Genetics RCV002486113 SCV002784925 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 2022-05-07 criteria provided, single submitter clinical testing
Breakthrough Genomics, Breakthrough Genomics RCV004692419 SCV005193022 uncertain significance not provided criteria provided, single submitter not provided

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