Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001751747 | SCV001574946 | pathogenic | not provided | 2022-09-06 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Cys335 amino acid residue in SCN5A. Other variant(s) that disrupt this residue have been observed in individuals with SCN5A-related conditions (PMID: 25650408, 30193851), which suggests that this may be a clinically significant amino acid residue. Advanced modeling of experimental studies (such as gene expression, population dynamics, functional pathways, and cell-cycle effects in cell culture) performed at Invitae indicates that this missense variant is expected to disrupt SCN5A protein function. ClinVar contains an entry for this variant (Variation ID: 1066556). This missense change has been observed in individuals with clinical features of Brugada syndrome (PMID: 28781330, 29402340; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 335 of the SCN5A protein (p.Cys335Arg). |
| Gene |
RCV001751747 | SCV001986390 | uncertain significance | not provided | 2019-04-09 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 28781330, 29402340, 32533946, 33131149) |