Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003509862 | SCV004245294 | pathogenic | 46,XY sex reversal 1 | 2023-06-14 | criteria provided, single submitter | clinical testing | The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Arg59Glnfs*45) in the SRY gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 146 amino acid(s) of the SRY protein. This variant has not been reported in the literature in individuals affected with SRY-related conditions. This variant disrupts a region of the SRY protein in which other variant(s) (p.Ile68Thr) have been determined to be pathogenic (PMID: 1438307). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |