Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV001841041 | SCV001355626 | uncertain significance | Cardiac arrhythmia | 2019-10-22 | criteria provided, single submitter | clinical testing | This variant causes a C>G nucleotide substitution at the +4 position of intron 20 of the SCN5A gene. Splice site prediction tools and conservation analysis are inconclusive regarding the impact of this variant on RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 7/246576 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Invitae | RCV002560023 | SCV003512530 | uncertain significance | Brugada syndrome | 2020-12-29 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 20 of the SCN5A gene. It does not directly change the encoded amino acid sequence of the SCN5A protein. It affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs539737269, ExAC 0.04%). This variant has not been reported in the literature in individuals with SCN5A-related conditions. ClinVar contains an entry for this variant (Variation ID: 926157). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |