Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000479877 | SCV000572755 | likely pathogenic | not provided | 2017-01-18 | criteria provided, single submitter | clinical testing | Although the c.4194delG likely pathogenic variant in the SCN5A gene has not been reported to our knowledge, this variant causes a shift in reading frame starting at codon valine (Val) 1400, changing it to a serine (Ser), and creating a premature stop codon at position 63 of the new reading frame, denoted p.Val1400SerfsX63. This pathogenic variant is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. Other frameshift variants in the SCN5A gene have been reported in the Human Gene Mutation Database in association with SCN5A-related disorders (Stenson et al., 2014). Furthermore, the c.4194delG variant was not observed in approximately 6,400 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. |
| Invitae | RCV000479877 | SCV001578819 | pathogenic | not provided | 2020-10-05 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in SCN5A are known to be pathogenic (PMID: 20129283, 22789973). This variant has not been reported in the literature in individuals with SCN5A-related conditions. ClinVar contains an entry for this variant (Variation ID: 423108). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Val1400Serfs*63) in the SCN5A gene. It is expected to result in an absent or disrupted protein product. |