Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001204751 | SCV001375972 | uncertain significance | Welander distal myopathy | 2019-09-13 | criteria provided, single submitter | clinical testing | 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. This variant disrupts the C-terminal region of the in TIA1 protein. Other variant(s) that disrupt this region (p.Glu384Lys) have been determined to be pathogenic (PMID: 23348830, 23401021). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with TIA1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the TIA1 gene (p.Gln366*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 21 amino acids of the TIA1 protein. |