Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000151808 | SCV000200274 | likely pathogenic | Brugada syndrome | 2014-01-31 | criteria provided, single submitter | clinical testing | The Phe86fs variant in SCN5A has not been previously reported in individuals wit h cardiomyopathy or in large population studies. This variant is predicted to c ause a frameshift, which alters the protein's amino acid sequence beginning at c odon 86 and leads to a premature stop codon 11 codons downstream. This alterati on is then predicted to lead to a truncated or absent protein. Heterozygous loss of function variants in the SCN5A gene have been reported in individuals with B rugada syndrome (Kapplinger 2010), DCM (Olson 2005), ventricular fibrillation (C hen 1998), as well as AV block and cardiac conduction defects (Baruteau 2012) bu t it is not clear if all variants of this type cause disease. In summary, this variant is very likely pathogenic but additional evidence is needed to establish this with certainty. |
| Labcorp Genetics |
RCV003764927 | SCV002225441 | pathogenic | not provided | 2022-03-29 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 165160). This sequence change creates a premature translational stop signal (p.Phe86Serfs*11) 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 variant has not been reported in the literature in individuals affected with SCN5A-related conditions. For these reasons, this variant has been classified as Pathogenic. |