Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000703435 | SCV000832334 | pathogenic | Diamond-Blackfan anemia | 2018-04-11 | criteria provided, single submitter | clinical testing | A different variant (c.386_387delGA) with the same protein effect as this variant (p.Asp130Serfs*23) has been determined to be pathogenic (PMID: 25946618). This suggests that disruption of this region of the RPS19 protein is causative of disease. This sequence change results in a frameshift in the RPS19 gene (p.Asp130Serfs*23). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 16 amino acids of the RPS19 protein and extend the protein by an additional 7 amino acids. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals and families with symptoms of Diamond-Blackfan anemia (PMID: 15075082, 10590074, 11112378, 15059149). This variant is also known as a deletion of c.383_384 in the literature. For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that deletion of the c-terminal portion of the RPS19 protein reduces protein stability and nuclear localization (PMID: 18768533). |