Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001893836 | SCV002171865 | benign | Hereditary nonpolyposis colorectal neoplasms | 2022-10-06 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002343987 | SCV002643174 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-01-10 | criteria provided, single submitter | clinical testing | The p.A40V variant (also known as c.119C>T), located in coding exon 1 of the MSH6 gene, results from a C to T substitution at nucleotide position 119. The alanine at codon 40 is replaced by valine, an amino acid with similar properties. This amino acid position is not 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. |
| All of Us Research Program, |
RCV004010817 | SCV004827964 | uncertain significance | Lynch syndrome | 2023-05-04 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with valine at codon 40 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 not been reported in individuals affected with MSH6-related disorders in the literature. This variant has been identified in 1/229582 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. |