Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001174627 | SCV001337833 | uncertain significance | not specified | 2020-01-20 | criteria provided, single submitter | clinical testing | Variant summary: RIT1 c.506A>G (p.Tyr169Cys) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.8e-05 in 251456 control chromosomes (gnomAD, exomes only). 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.506A>G in individuals affected with Noonan Syndrome and Related Conditions and no experimental evidence demonstrating its impact on protein function have been reported. 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 uncertain significance. |
Invitae | RCV001323575 | SCV001514497 | uncertain significance | Noonan syndrome 8 | 2020-03-19 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine with cysteine at codon 169 of the RIT1 protein (p.Tyr169Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). This variant has not been reported in the literature in individuals with RIT1-related conditions. This variant is present in population databases (rs763208084, ExAC 0.03%). |
Genome- |
RCV001323575 | SCV004050443 | uncertain significance | Noonan syndrome 8 | 2023-04-11 | criteria provided, single submitter | clinical testing |