Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001064225 | SCV001229111 | pathogenic | Diamond-Blackfan anemia | 2019-12-16 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Thr5Asnfs*46) in the RPS19 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) and a stillborn fetus affected with Diamond-Blackfan anaemia (PMID: 9988267, 23349008). Loss-of-function variants in RPS19 are known to be pathogenic (PMID: 20960466). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV001064225 | SCV002697730 | pathogenic | Diamond-Blackfan anemia | 2018-06-04 | criteria provided, single submitter | clinical testing | The c.13dupA pathogenic mutation, located in coding exon 1 of the RPS19 gene, results from a duplication of A at nucleotide position 13, causing a translational frameshift with a predicted alternate stop codon (p.T5Nfs*46). This mutation was identified in one individual with Diamond-Blackfan anemia (DBA) (Draptchinskaia N et al. Nat. Genet., 1999 Feb;21:169-75). Cultured cells from a transfusion dependent individual with DBA demonstrated reduced RPS19 mRNA levels (Chatr-Aryamontri A et al. Hum. Mutat., 2004 Dec;24:526-33). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |