Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000695645 | SCV000824157 | uncertain significance | Noonan syndrome | 2018-01-24 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with cysteine at codon 56 of the RRAS protein (p.Ser56Cys). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and cysteine. 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. |
St. |
RCV000695645 | SCV003928040 | uncertain significance | Noonan syndrome | 2023-05-10 | criteria provided, single submitter | clinical testing | The RRAS c.167C>G (p.Ser56Cys) missense change has a maximum subpopulation frequency of 0.01% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function, and to our knowledge functional studies have not been performed. To our knowledge, this variant has not been reported in individuals with Noonan syndrome. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003403613 | SCV004121896 | uncertain significance | not specified | 2023-10-19 | criteria provided, single submitter | clinical testing |