Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000630015 | SCV000750971 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2023-12-18 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000771661 | SCV000904285 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-01-04 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with serine at codon 1086 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 an individual affected with urothelial carcinoma (PMID: 36091175) . This variant has been identified in 1/251438 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. |
Ambry Genetics | RCV000771661 | SCV002611013 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-05-02 | criteria provided, single submitter | clinical testing | The p.P1086S variant (also known as c.3256C>T), located in coding exon 5 of the MSH6 gene, results from a C to T substitution at nucleotide position 3256. The proline at codon 1086 is replaced by serine, an amino acid with similar properties. 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 |
RCV003332215 | SCV004039691 | uncertain significance | not provided | 2023-09-17 | 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; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 17531815, 21120944) |
All of Us Research Program, |
RCV004002789 | SCV004835024 | uncertain significance | Lynch syndrome | 2023-10-06 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with serine at codon 1086 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 an individual affected with urothelial carcinoma (PMID: 36091175) . This variant has been identified in 1/251438 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. |