Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000230625 | SCV000284181 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2024-01-27 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000564902 | SCV000669798 | likely benign | Hereditary cancer-predisposing syndrome | 2022-07-11 | 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. |
Color Diagnostics, |
RCV000564902 | SCV000685127 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-02 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamine with arginine at codon 252 of the MSH2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). This variant does not impact MSH2 function in a 6-thioguanine sensitivity assay in haploid human cells (internally defined LOF score threshold <= -1.32, PMID: 33357406). This variant has been reported in an individual affected with breast cancer (PMID: 25186627). This variant has been identified in 1/251402 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Gene |
RCV001557291 | SCV001779026 | uncertain significance | not provided | 2023-11-08 | criteria provided, single submitter | clinical testing | Observed in an individual with breast cancer (PMID: 25186627); Published functional studies suggest a neutral effect: demonstrates sensitivity to 6-TG and mismatch repair (MMR) function similar to wild-type (PMID: 33357406); In silico analysis supports that this missense variant does not alter protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25186627, 33357406, 18822302, 21120944) |
Sema4, |
RCV000564902 | SCV002526740 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-04-30 | criteria provided, single submitter | curation | |
Baylor Genetics | RCV003463649 | SCV004196236 | uncertain significance | Lynch syndrome 1 | 2023-09-23 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV003998764 | SCV004829082 | uncertain significance | Lynch syndrome | 2024-02-05 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamine with arginine at codon 252 of the MSH2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). This variant does not impact MSH2 function in a 6-thioguanine sensitivity assay in haploid human cells (internally defined LOF score threshold <= -1.32, PMID: 33357406). This variant has been reported in an individual affected with breast cancer (PMID: 25186627). This variant has been identified in 1/251402 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |