Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000697940 | SCV000826574 | uncertain significance | Noonan syndrome | 2023-06-18 | criteria provided, single submitter | clinical testing | 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 575657). This variant has not been reported in the literature in individuals affected with RRAS-related conditions. This variant is present in population databases (rs373359206, gnomAD 0.08%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces glycine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 17 of the RRAS protein (p.Gly17Trp). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001824868 | SCV002074160 | uncertain significance | not specified | 2022-01-09 | criteria provided, single submitter | clinical testing | Variant summary: RRAS c.49G>T (p.Gly17Trp) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 5.4e-05 in 92070 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.49G>T in individuals affected with Noonan Syndrome And Related Conditions and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Ambry Genetics | RCV002334338 | SCV002640676 | uncertain significance | Inborn genetic diseases | 2021-07-01 | criteria provided, single submitter | clinical testing | The p.G17W variant (also known as c.49G>T), located in coding exon 1 of the RRAS gene, results from a G to T substitution at nucleotide position 49. The glycine at codon 17 is replaced by tryptophan, an amino acid with highly dissimilar 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. |