Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000590334 | SCV000700028 | likely pathogenic | Brugada syndrome (shorter-than-normal QT interval) | 2016-12-12 | criteria provided, single submitter | clinical testing | Variant summary: The SCN5A c.3946C>T (p.Arg1316X) variant results in a premature termination codon, predicted to cause a truncated or absent SCN5A protein due to nonsense mediated decay. The variant of interest was not found in controls (ExAC, 1000 Gs, ESP, or published controls) and has been reported in an affected individual diagnosed with Brugada Syndrome via a publication. However, no clinical diagnostic and/or databases have cited the variant. Therefore, the variant of interest has been classified as "likely pathogenic." |
| Invitae | RCV000681957 | SCV001399379 | pathogenic | not provided | 2023-11-08 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg1316*) in the SCN5A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SCN5A are known to be pathogenic (PMID: 20129283, 22789973). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with Brugada syndrome (PMID: 19561025, 30828344). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 496571). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV000681957 | SCV001756144 | pathogenic | not provided | 2020-08-26 | criteria provided, single submitter | clinical testing | Reported in ClinVar as likely pathogenic and pathogenic (ClinVar Variant ID# 496571; Landrum et al., 2016); Not observed in large population cohorts (Lek et al., 2016); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 31447099, 30828344, 19561025) |
| Clinical Genetics Laboratory, |
RCV001839456 | SCV002099539 | likely pathogenic | Brugada syndrome 1 | 2021-02-18 | criteria provided, single submitter | clinical testing | PVS1, PM2 |
| Gharavi Laboratory, |
RCV000681957 | SCV000809452 | likely pathogenic | not provided | 2018-09-16 | no assertion criteria provided | research |