Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000526049 | SCV000625441 | benign | Hereditary nonpolyposis colorectal neoplasms | 2023-11-17 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000579804 | SCV000685110 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-20 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with glutamine at codon 205 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). A functional study has reported the variant protein as normal for in vitro DNA mismatch repair assay (PMID: 22581703, 19728162). This variant also 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 observed in an individual affected with pancreatic cancer (PMID: 19728162). This variant has been identified in 5/282284 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. |
Ambry Genetics | RCV000579804 | SCV001187029 | likely benign | Hereditary cancer-predisposing syndrome | 2022-07-13 | 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. |
Gene |
RCV001584241 | SCV001812505 | likely benign | not provided | 2020-12-02 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 29641532, 22581703, 19728162) |
All of Us Research Program, |
RCV004003753 | SCV004830828 | uncertain significance | Lynch syndrome | 2023-09-17 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with glutamine at codon 205 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). A functional study has reported the variant protein as normal for in vitro DNA mismatch repair assay (PMID: 22581703, 19728162). This variant also 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 observed in an individual affected with pancreatic cancer (PMID: 19728162). This variant has been identified in 5/282284 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. |