Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000491118 | SCV000580591 | likely benign | Hereditary cancer-predisposing syndrome | 2023-05-11 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000985813 | SCV001134368 | uncertain significance | not provided | 2019-01-22 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001053469 | SCV001217733 | benign | Hereditary nonpolyposis colorectal neoplasms | 2024-01-12 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001532970 | SCV001748794 | uncertain significance | not specified | 2021-06-28 | criteria provided, single submitter | clinical testing | Variant summary: MSH2 c.509A>G (p.Gln170Arg) results in a conservative amino acid change located in the DNA mismatch repair protein MutS, connector domain of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251484 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.509A>G in individuals affected with Lynch Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Gene |
RCV000985813 | SCV002002629 | uncertain significance | not provided | 2021-02-25 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| All of Us Research Program, |
RCV004003472 | SCV004821992 | uncertain significance | Lynch syndrome | 2023-06-28 | criteria provided, single submitter | clinical testing |