Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001222578 | SCV001394683 | pathogenic | Diamond-Blackfan anemia | 2019-07-23 | criteria provided, single submitter | clinical testing | This variant has been observed in an individual affected with refractory transfusion dependent anemia (Invitae). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the RPS19 protein. Experimental studies have shown that deletion of the C-terminal portion of the RPS19 protein reduces protein stability and nuclear localization (PMID: 18768533). Moreover, other variant(s) that disrupt this region (p.Ala100Trpfs*12, p.Gln128*) have been determined to be pathogenic (PMID: 12750732, Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the RPS19 gene (p.Val87Argfs*67). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 59 amino acids of the RPS19 protein. |