Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002512845 | SCV003443917 | likely pathogenic | Diamond-Blackfan anemia | 2022-01-12 | criteria provided, single submitter | clinical testing | This missense change has been observed in individuals with clinical features of Diamond-Blackfan anemia (PMID: 10590074, 31574871; Invitae). This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 127 of the RPS19 protein (p.Gly127Glu). This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 6320). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects RPS19 function (PMID: 12586610, 17517689, 18768533). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
OMIM | RCV000033189 | SCV000057025 | pathogenic | Diamond-Blackfan anemia 1 | 2007-07-15 | no assertion criteria provided | literature only |