Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001066690 | SCV001231706 | pathogenic | Diamond-Blackfan anemia | 2022-07-29 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 860401). This sequence change affects the initiator methionine of the RPS19 mRNA. The next in-frame methionine is located at codon 75. This variant is not present in population databases (gnomAD no frequency). Disruption of the initiator codon has been observed in individuals with Diamond-Blackfan anemia (PMID: 12750732, 20378560, 20603584, 27329125, 28102861, 28376382). This variant is also known as ATG3ATA, g.3G>A. |
| Ambry Genetics | RCV001066690 | SCV002619596 | pathogenic | Diamond-Blackfan anemia | 2017-04-20 | criteria provided, single submitter | clinical testing | The p.M1? pathogenic mutation (also known as c.3G>A) is located in coding exon 1 of the RPS19 gene and results from a G to A substitution at nucleotide position 3. This alters the methionine residue at the initiation codon. This mutation was detected in multiple individuals with Diamond-Blackfan anemia (Proust A et al. Hematol. J., 2003;4:132-6; Chae H et al. Exp. Mol. Med., 2014 Mar;46:e88; Delaporta P et al. Pediatr Blood Cancer, 2014 Dec;61:2249-55). In addition, two mutations at the same codon, c.3G>C and c.3G>T, were reported in affected individuals (Ramenghi U et al. Blood Cells Mol. Dis., 2000 Oct;26:417-22; Orfali KA et al. Br. J. Haematol., 2004 Apr;125:243-52). In addition to the clinical data presented in the literature, since sequence variations that modify the initiation codon (ATG) are expected to result in either loss of translation initiation, N-terminal truncation, or cause a shift in the mRNA reading frame, this alteration is interpreted as a disease-causing mutation. |