Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001841098 | SCV001357416 | likely pathogenic | Cardiac arrhythmia | 2018-10-23 | criteria provided, single submitter | clinical testing | Likely Pathogenic variant based on current evidence: This variant causes a duplication of 8 nucleotides at the exon 22-intron 22 boundary and alters the canonical splice donor site in intron 22 of the SCN5A gene. Computational splicing tools predict that this variant may have a significant impact on mRNA splicing. Although RNA study has not been performed to confirm the prediction, this variant is expected to result in an absent or disrupted protein product. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant is rare in the general population and has been identified in 0/277264 chromosomes by the Genome Aggregation Database (gnomAD). Loss of SCN5A function is a known mechanism of disease. Although additional studies are required to fully establish its clinical significance, based on available evidence, this variant is classified as Likely Pathogenic. |
| Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, |
RCV001256853 | SCV001433341 | likely pathogenic | not provided | 2019-11-21 | criteria provided, single submitter | clinical testing | |
| Laboratory for Molecular Medicine, |
RCV004017796 | SCV004847593 | likely pathogenic | Brugada syndrome | 2018-10-22 | criteria provided, single submitter | clinical testing | The c.3957_3963+1dupCATGAGGG variant in SCN5A has not been previously reported in individuals with Brugada syndrome and was absent from large population studies. This variant impacts the 5' canonical splice site of intron 22 and is predicted to alter splicing and introduce a premature termination codon, which would result in an abnormal or absent protein. Loss of function of the SCN5A gene is an established disease mechanism in autosomal dominant Brugada syndrome. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal dominant Brugada syndrome. ACMG/AMP Criteria applied: PVS1, PM2. |