Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Athena Diagnostics Inc | RCV000713092 | SCV000843660 | pathogenic | not provided | 2016-06-08 | criteria provided, single submitter | clinical testing | |
Institute Of Human Genetics Munich, |
RCV001254163 | SCV001430119 | pathogenic | Paramyotonia congenita of Von Eulenburg | 2020-07-01 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000713092 | SCV001500144 | pathogenic | not provided | 2020-10-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000206954 | SCV001588729 | pathogenic | Hyperkalemic periodic paralysis | 2023-12-18 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 675 of the SCN4A protein (p.Arg675Trp). This variant is present in population databases (rs121908556, gnomAD 0.003%). This missense change has been observed in individuals with autosomal dominant SCN4A-related conditions (PMID: 15596759, 29606556). ClinVar contains an entry for this variant (Variation ID: 5902). 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%. Experimental studies have shown that this missense change affects SCN4A function (PMID: 19052238). This variant disrupts the p.Arg675 amino acid residue in SCN4A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15596759, 19052238, 22926674). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
Revvity Omics, |
RCV000713092 | SCV002019137 | likely pathogenic | not provided | 2020-03-21 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000713092 | SCV002599598 | likely pathogenic | not provided | 2023-02-06 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Different missense changes at this residue (R675G) and (R675Q) have been reported in the Human Gene Mutation Database (Stenson et al., 2014); This variant is associated with the following publications: (PMID: 31708864, 19201608, 19052238, 29606556, 22016737, 32962503, 24772081, 20301669, 29930533, 22926674, 15596759) |
OMIM | RCV000006263 | SCV000026445 | pathogenic | Normokalemic periodic paralysis, potassium-sensitive | 2004-12-14 | no assertion criteria provided | literature only | |
Gene |
RCV000206954 | SCV000262568 | not provided | Hyperkalemic periodic paralysis | no assertion provided | literature only |