Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000685059 | SCV000812531 | uncertain significance | Noonan syndrome | 2018-06-26 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with RRAS-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with valine at codon 217 of the RRAS protein (p.Leu217Val). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and valine. |
| Ambry Genetics | RCV004857726 | SCV005493765 | uncertain significance | not specified | 2024-12-07 | criteria provided, single submitter | clinical testing | The p.L217V variant (also known as c.649C>G), located in coding exon 6 of the RRAS gene, results from a C to G substitution at nucleotide position 649. The leucine at codon 217 is replaced by valine, 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. Based on the available evidence, the clinical significance of this variant remains unclear. |