Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000227011 | SCV000283742 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2024-01-17 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000483631 | SCV000565222 | uncertain significance | not provided | 2023-05-09 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in at least one individual referred for hereditary cancer testing (Paulo et al., 2017); This variant is associated with the following publications: (PMID: 17531815, 21120944, 28529006) |
Color Diagnostics, |
RCV000580465 | SCV000685257 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-06 | criteria provided, single submitter | clinical testing | This missense variant replaces methionine with valine at codon 703 of the MSH6 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). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MSH6-related disorders in the literature. This variant has been identified in 4/276460 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 | RCV000662419 | SCV000784855 | uncertain significance | Lynch syndrome 5 | 2017-01-11 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000662419 | SCV001135815 | uncertain significance | Lynch syndrome 5 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000580465 | SCV001175163 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-09 | criteria provided, single submitter | clinical testing | The p.M703V variant (also known as c.2107A>G), located in coding exon 4 of the MSH6 gene, results from an A to G substitution at nucleotide position 2107. The methionine at codon 703 is replaced by valine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Institute for Clinical Genetics, |
RCV000483631 | SCV002010109 | uncertain significance | not provided | 2021-11-03 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV000662419 | SCV004018449 | uncertain significance | Lynch syndrome 5 | 2023-03-27 | 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 | RCV003469132 | SCV004195569 | uncertain significance | Endometrial carcinoma | 2023-08-21 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV003998715 | SCV004843857 | uncertain significance | Lynch syndrome | 2023-12-07 | criteria provided, single submitter | clinical testing | This missense variant replaces methionine with valine at codon 703 of the MSH6 protein. Computational prediction tool 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). To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 4/276460 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. |