Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000205023 | SCV000259599 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2024-01-24 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000565881 | SCV000662208 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-10-26 | criteria provided, single submitter | clinical testing | The p.L312V variant (also known as c.934C>G), located in coding exon 5 of the MSH2 gene, results from a C to G substitution at nucleotide position 934. The leucine at codon 312 is replaced by valine, an amino acid with highly similar properties. In a massively parallel cell-based functional assay testing susceptibility to a DNA damaging agent, 6-thioguanine (6-TG), this variant was reported to be functionally neutral (Jia X et al. Am J Hum Genet, 2021 01;108:163-175). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Color Diagnostics, |
RCV000565881 | SCV000690141 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-05 | criteria provided, single submitter | clinical testing | This missense variant replaces leucine with valine at codon 312 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 individuals affected with MSH2-related disorders in the literature. This variant has been identified in 2/215192 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. |
Counsyl | RCV000662459 | SCV000784940 | uncertain significance | Lynch syndrome 1 | 2017-02-09 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV000662459 | SCV004018280 | 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. |
All of Us Research Program, |
RCV003997573 | SCV004824375 | uncertain significance | Lynch syndrome | 2023-12-01 | criteria provided, single submitter | clinical testing | This missense variant replaces leucine with valine at codon 312 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 individuals affected with MSH2-related disorders in the literature. This variant has been identified in 2/215192 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. |