Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002230416 | SCV000551203 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2023-10-15 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002436447 | SCV002751534 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-15 | criteria provided, single submitter | clinical testing | The p.R988P variant (also known as c.2963G>C), located in coding exon 4 of the MSH6 gene, results from a G to C substitution at nucleotide position 2963. The arginine at codon 988 is replaced by proline, an amino acid with dissimilar properties. This amino acid position is not well 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. |
All of Us Research Program, |
RCV004001842 | SCV004830000 | uncertain significance | Lynch syndrome | 2023-09-09 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with proline at codon 988 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 1/217126 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. |