Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000182989 | SCV000235390 | pathogenic | not provided | 2011-09-01 | criteria provided, single submitter | clinical testing | Although the c.1891-1 G>A mutation in the SCN5A gene has not been reported previously to our knowledge, this mutation destroys the consensus splice acceptor site of intron 12 and is expected to cause abnormal gene splicing. This is predicted to lead to either an abnormal message which is subject to nonsense-mediated mRNA decay or to an abnormal protein product if the message is used for protein translation. In addition, c.1891-1 G>A was not present in up to 400 alleles from control individuals of Caucasian and African American ancestry tested at GeneDx, indicating it is not a common benign variant in these populations. Furthermore, other splice mutations in the SCN5A gene have been reported in association with Brugada syndrome. The variant is found in BRUGADA panel(s). |
Labcorp Genetics |
RCV000182989 | SCV004426522 | likely pathogenic | not provided | 2023-01-17 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. ClinVar contains an entry for this variant (Variation ID: 201464). This variant has not been reported in the literature in individuals affected with SCN5A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 12 of the SCN5A gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SCN5A are known to be pathogenic (PMID: 20129283, 22789973). |