Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002406012 | SCV002710991 | likely pathogenic | Diamond-Blackfan anemia | 2018-05-17 | criteria provided, single submitter | clinical testing | The p.R56L variant (also known as c.167G>T), located in coding exon 2 of the RPS19 gene, results from a G to T substitution at nucleotide position 167. The arginine at codon 56 is replaced by leucine, an amino acid with dissimilar properties. RPS19 is a ribosomal protein and it binds directly to DNA; R56 is shown by crystal structure to directly interact with the DNA-backbone (Yamamoto H, EMBO J. 2015 Dec; 34(24):3042-58.) In addition, an alteration at the same amino acid position, p.R56Q, has been described in multiple families with Diamond-Blackfan anemia (Willig TN et al, Blood 1999 Dec; 94(12):4294-306). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis.Based on the majority of available evidence to date, this variant is likely to be pathogenic. |