ClinVar Miner

Submissions for variant NM_000334.4(SCN4A):c.2419G>A (p.Ala807Thr)

gnomAD frequency: 0.00004  dbSNP: rs770694096
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000694016 SCV000822441 uncertain significance Hyperkalemic periodic paralysis 2024-05-22 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 807 of the SCN4A protein (p.Ala807Thr). This variant is present in population databases (rs770694096, gnomAD 0.03%). 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: 572594). 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.
Athena Diagnostics RCV000992891 SCV001145477 likely benign not provided 2019-04-12 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000992891 SCV003821265 uncertain significance not provided 2020-05-20 criteria provided, single submitter clinical testing
Ambry Genetics RCV003303139 SCV004000086 uncertain significance Inborn genetic diseases 2023-05-09 criteria provided, single submitter clinical testing The c.2419G>A (p.A807T) alteration is located in exon 14 (coding exon 14) of the SCN4A gene. This alteration results from a G to A substitution at nucleotide position 2419, causing the alanine (A) at amino acid position 807 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV005021070 SCV005651787 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 2024-06-03 criteria provided, single submitter clinical testing

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