Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001892244 | SCV002151893 | uncertain significance | Noonan syndrome | 2021-08-04 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with methionine at codon 55 of the RRAS protein (p.Val55Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies have shown that this variant affects RRAS protein function (PMID: 24705357). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been observed in individual(s) with clinical features of RRAS-related conditions (PMID: 24705357). This variant is present in population databases (rs368625677, ExAC 0.02%). |