Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000702591 | SCV000831450 | uncertain significance | Noonan syndrome | 2018-03-15 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine with phenylalanine at codon 53 of the RRAS protein (p.Tyr53Phe). The tyrosine residue is highly conserved and there is a small physicochemical difference between tyrosine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with RRAS-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function 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. |
Ambry Genetics | RCV004026600 | SCV005016134 | uncertain significance | not specified | 2024-03-31 | criteria provided, single submitter | clinical testing | The p.Y53F variant (also known as c.158A>T), located in coding exon 2 of the RRAS gene, results from an A to T substitution at nucleotide position 158. The tyrosine at codon 53 is replaced by phenylalanine, 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 alteration remains unclear. |