Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV004521045 | SCV005037008 | likely pathogenic | Diamond-Blackfan anemia | 2017-05-03 | criteria provided, single submitter | clinical testing | The p.A57P variant (also known as c.169G>C), located in coding exon 2 of the RPS19 gene, results from a G to C substitution at nucleotide position 169. The alanine at codon 57 is replaced by proline, an amino acid with highly similar properties. This mutation was reported in one individual with Diamond-Blackfan anemia (Orfali KA et al. Br. J. Haematol., 2004 Apr;125:243-52). In addition, in vitro studies showed nearly undetectable mutant protein in HEK293 cells that did not associate with ribosomes (Angelini M et al. Hum. Mol. Genet., 2007 Jul;16:1720-7). Structural analysis revealed that this variant is located in the hydrophobic core of an alpha helix and is predicted to impact folding and stability of the RPS19 protein. (Gregory LA et al. Nucleic Acids Res., 2007 Aug;35:5913-21). This amino acid position is highly 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. |