Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000220354 | SCV000276256 | likely benign | Hereditary cancer-predisposing syndrome | 2023-03-21 | 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. |
Invitae | RCV000232111 | SCV000284087 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2024-01-25 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000236110 | SCV000293975 | uncertain significance | not provided | 2023-09-07 | criteria provided, single submitter | clinical testing | Observed in an individual with colorectal cancer whose tumor demonstrated microsatellite instability and loss of MSH2/MSH6 expression, as well as in individuals with endometrial, breast cancer, or osteosarcoma (Rodrguez-Soler et al., 2013; Yehia et al., 2018; Mirabello et al., 2020; Bhai et al., 2021); Published functional studies demonstrate mismatch repair function similar to wildtype (Jia et al., 2020); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23354017, 22144684, 29684080, 26344056, 18822302, 21120944, 32191290, 34326862, 32522261, 33357406) |
Counsyl | RCV000662429 | SCV000784883 | uncertain significance | Lynch syndrome 1 | 2017-01-17 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000220354 | SCV000908289 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-26 | criteria provided, single submitter | clinical testing | This missense variant replaces leucine with valine at codon 341 of the MSH2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 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 colorectal cancer that exhibited loss of MSH2 and MSH6 proteins by immunohistochemistry analyses (PMID: 23354017). This variant has been identified in 7/251452 chromosomes in the general population by the Genome Aggregation Database (gnomAD). A different variant affecting the same codon, c.1022T>C (p.Leu341Pro), is considered to be disease-causing (ClinVar variation ID: 234622), suggesting that this position is important for the protein function. 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. |
Myriad Genetics, |
RCV000662429 | SCV004043995 | likely benign | Lynch syndrome 1 | 2023-05-08 | criteria provided, single submitter | clinical testing | This variant is considered likely benign. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic variants in this gene [PMID: 25085752]. |
Baylor Genetics | RCV000662429 | SCV004196837 | uncertain significance | Lynch syndrome 1 | 2023-05-17 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV003997950 | SCV004824554 | uncertain significance | Lynch syndrome | 2023-12-13 | criteria provided, single submitter | clinical testing | This missense variant replaces leucine with valine at codon 341 of the MSH2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 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 not been reported in an individual affected with colorectal cancer that exhibited loss of MSH2 and MSH6 proteins by immunohistochemistry analyses (PMID: 23354017). This variant has been identified in 7/251452 chromosomes in the general population by the Genome Aggregation Database (gnomAD). A different variant affecting the same codon, c.1022T>C (p.Leu341Pro), is considered to be disease-causing (ClinVar variation ID: 234622), suggesting that this position is important for the protein function. 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. |