Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001264469 | SCV001442642 | uncertain significance | not specified | 2020-10-19 | criteria provided, single submitter | clinical testing | Variant summary: RRAS c.562C>T (p.Arg188Trp) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 246912 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow clear conclusions about variant significance. To our knowledge, no occurrence of c.562C>T in individuals affected with Noonan Syndrome and Related Conditions and no experimental evidence demonstrating its impact on protein function have been reported. Another variant affecting the same amino acid residue (c.563G>A (p.Arg188Gln)) is classified as benign by our laboratory. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as VUS-possibly benign. |
Labcorp Genetics |
RCV001315165 | SCV001505723 | uncertain significance | Noonan syndrome | 2022-07-19 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs538230538, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 188 of the RRAS protein (p.Arg188Trp). This variant has not been reported in the literature in individuals affected with RRAS-related conditions. ClinVar contains an entry for this variant (Variation ID: 984470). 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. 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. |