Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002374128 | SCV002688391 | likely pathogenic | Cardiovascular phenotype | 2020-11-30 | criteria provided, single submitter | clinical testing | The p.Q32* variant (also known as c.94C>T), located in coding exon 1 of the SCN5A gene, results from a C to T substitution at nucleotide position 94. This changes the amino acid from a glutamine to a stop codon within coding exon 1. The predicted stop codon occurs within the first 150 nucleotides of theSCN5A gene. This alteration may escape nonsense-mediated mRNAdecay and/or be rescued by re-initiation (Rivas et al. Science. 2015 May 8;348(6235):666-9; Lindeboom et al. Nat Genet. 2016 Oct;48(10):1112-8; Rhee et al. Sci Rep. 2017 May 10;7(1):1653). However, the impacted region is critical for protein function (Ambry internal data). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Invitae | RCV003546813 | SCV004262250 | pathogenic | not provided | 2023-12-29 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln32*) in the SCN5A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SCN5A are known to be pathogenic (PMID: 20129283, 22789973). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SCN5A-related conditions. ClinVar contains an entry for this variant (Variation ID: 1767167). For these reasons, this variant has been classified as Pathogenic. |