ClinVar Miner

Submissions for variant NM_000334.4(SCN4A):c.2662A>C (p.Lys888Gln)

gnomAD frequency: 0.00005  dbSNP: rs202155883
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000559969 SCV000658539 uncertain significance Hyperkalemic periodic paralysis 2024-01-15 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 888 of the SCN4A protein (p.Lys888Gln). This variant is present in population databases (rs202155883, gnomAD 0.005%). 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: 477407). 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 not expected to disrupt SCN4A protein function with a negative 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 RCV005004245 SCV002796977 uncertain significance Potassium-aggravated myotonia; Paramyotonia congenita of Von Eulenburg; Hypokalemic periodic paralysis, type 2; Hyperkalemic periodic paralysis; Congenital myasthenic syndrome 16; Congenital myopathy 22A, classic; Congenital myopathy 22B, severe fetal 2024-05-09 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV003139862 SCV003821276 uncertain significance not provided 2022-09-08 criteria provided, single submitter clinical testing
Ambry Genetics RCV004024398 SCV004944257 uncertain significance Inborn genetic diseases 2023-12-12 criteria provided, single submitter clinical testing The c.2662A>C (p.K888Q) alteration is located in exon 14 (coding exon 14) of the SCN4A gene. This alteration results from a A to C substitution at nucleotide position 2662, causing the lysine (K) at amino acid position 888 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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