Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV004050479 | SCV002622972 | uncertain significance | not specified | 2021-11-24 | criteria provided, single submitter | clinical testing | The p.R132H variant (also known as c.395G>A), located in coding exon 4 of the RRAS gene, results from a G to A substitution at nucleotide position 395. The arginine at codon 132 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Labcorp Genetics |
RCV003094460 | SCV003252866 | uncertain significance | Noonan syndrome | 2022-04-07 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 132 of the RRAS protein (p.Arg132His). This variant is present in population databases (rs142277653, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with RRAS-related conditions. 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: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. |