Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000215096 | SCV000277875 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-27 | criteria provided, single submitter | clinical testing | The p.I251V variant (also known as c.751A>G), located in coding exon 4 of the MSH6 gene, results from an A to G substitution at nucleotide position 751. The isoleucine at codon 251 is replaced by valine, an amino acid with highly similar properties. This alteration was detected in 1/136 families with breast and colon cancer and in 0/332 controls (Wasielewski M et al. Breast Cancer Res Treat. 2010 Sep;123(2):315-20). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Gene |
RCV000220612 | SCV000279608 | uncertain significance | not provided | 2023-08-26 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in individuals with hereditary breast and colon cancer and in 3 sisters with pancreatic and/or thyroid cancer (Wasielewski et al., 2010; Milella et al., 2022); This variant is associated with the following publications: (PMID: 23621914, 29596542, 22290698, 26333163, 21437237, 19924528, 35901820, 26635394) |
Invitae | RCV000630227 | SCV000751183 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2024-01-02 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000662409 | SCV000784839 | uncertain significance | Lynch syndrome 5 | 2017-01-04 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000215096 | SCV000911421 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-02 | criteria provided, single submitter | clinical testing | This missense variant replaces isoleucine with valine at codon 251 of the MSH6 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 a family affected with hereditary breast and colorectal cancer (PMID: 19924528), and in related individuals affected with pancreatic and thyroid cancer (PMID: 35901820). This variant has been identified in 2/251160 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, |
RCV000662409 | SCV004019060 | uncertain significance | Lynch syndrome 5 | 2023-03-29 | 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 | RCV003460703 | SCV004197576 | uncertain significance | Endometrial carcinoma | 2023-10-26 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV003997102 | SCV004836997 | uncertain significance | Lynch syndrome | 2023-11-20 | criteria provided, single submitter | clinical testing | This missense variant replaces isoleucine with valine at codon 251 of the MSH6 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 a family affected with hereditary breast and colorectal cancer (PMID: 19924528), and in related individuals affected with pancreatic and thyroid cancer (PMID: 35901820). This variant has been identified in 2/251160 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. |