Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000182928 | SCV000235323 | pathogenic | not provided | 2022-04-25 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); Canonical splice site variant expected to result in aberrant splicing, although in the absence of functional evidence the actual effect of this sequence change is unknown |
Laboratory for Molecular Medicine, |
RCV000604031 | SCV000712497 | likely pathogenic | Brugada syndrome; Congenital long QT syndrome | 2016-10-28 | criteria provided, single submitter | clinical testing | The c.483-1G>A variant in SCN5A has not been previously reported in individuals with SCN5A-associated channelopathies or in large population studies. This varia nt occurs in the invariant region (+/- 1,2) of the splice consensus sequence and is predicted to cause altered splicing leading to an abnormal or absent protein . Loss of function variants in SCN5A are most commonly associated with Brugada s yndrome although overlap presentations including other SCN5A-related phenotypes (Long QT syndrome) have been described (Remme 2013). In summary, although additi onal studies are required to fully establish its clinical significance, the c.48 3-1G>A variant is likely pathogenic. |
Invitae | RCV000182928 | SCV001397612 | likely pathogenic | not provided | 2022-12-25 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 201432). 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 4 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). |
Molecular Genetics Laboratory, |
RCV001225336 | SCV004015012 | likely pathogenic | Brugada syndrome | 2023-01-24 | no assertion criteria provided | clinical testing |