Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics Inc | RCV000518217 | SCV000615086 | likely pathogenic | not provided | 2017-04-20 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000545880 | SCV000658561 | likely pathogenic | Hyperkalemic periodic paralysis | 2022-05-06 | criteria provided, single submitter | clinical testing | Experimental studies have shown that this missense change affects SCN4A function (PMID: 27164696). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1158 of the SCN4A protein (p.Pro1158Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with myotonia permanens (PMID: 27164696). ClinVar contains an entry for this variant (Variation ID: 448275). 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: "Probably Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Pro1158 amino acid residue in SCN4A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10851391, 21221019). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |