Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000166585 | SCV000217387 | likely benign | Hereditary cancer-predisposing syndrome | 2022-08-22 | 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 | RCV000205937 | SCV000260599 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2023-04-25 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs772052262, gnomAD 0.002%). This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 146 of the MSH2 protein (p.Gly146Val). This missense change has been observed in individual(s) with endometrial cancer (PMID: 28051113). 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. Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 33357406) indicates that this missense variant is not expected to disrupt MSH2 function. ClinVar contains an entry for this variant (Variation ID: 186918). |
Counsyl | RCV000662555 | SCV000785139 | uncertain significance | Lynch syndrome 1 | 2017-05-15 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000166585 | SCV001350531 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-01 | criteria provided, single submitter | clinical testing | This missense variant replaces glycine with valine at codon 146 of the MSH2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with endometrial cancer (PMID: 28051113) This variant has been identified in 1/251434 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. |
Myriad Genetics, |
RCV000662555 | SCV004018266 | uncertain significance | Lynch syndrome 1 | 2023-03-17 | criteria provided, single submitter | clinical testing | This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk. |
Baylor Genetics | RCV000662555 | SCV004196315 | uncertain significance | Lynch syndrome 1 | 2023-08-12 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV003995514 | SCV004830266 | uncertain significance | Lynch syndrome | 2023-10-30 | criteria provided, single submitter | clinical testing | This missense variant replaces glycine with valine at codon 146 of the MSH2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with endometrial cancer (PMID: 28051113) This variant has been identified in 1/251434 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. |