Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000521551 | SCV000618745 | likely pathogenic | not provided | 2018-06-15 | criteria provided, single submitter | clinical testing | The Q24X variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Although the Q24X variant has not been previously reported to our knowledge, other nonsense variants in the TPM2 gene have been previously reported in the Human Gene Mutation Database in association with TPM2-related disorders (Stenson et al., 2014). |
| Invitae | RCV001201905 | SCV001372996 | pathogenic | Arthrogryposis, distal, type 1A | 2019-10-24 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in TPM2 are known to be pathogenic (PMID: 19155175, 27726070). 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 TPM2-related conditions. ClinVar contains an entry for this variant (Variation ID: 450194). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln24*) in the TPM2 gene. It is expected to result in an absent or disrupted protein product. |