Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000542898 | SCV000625008 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2023-11-07 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000567017 | SCV000669896 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-14 | criteria provided, single submitter | clinical testing | The p.S28L variant (also known as c.83C>T), located in coding exon 1 of the MSH6 gene, results from a C to T substitution at nucleotide position 83. The serine at codon 28 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is 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. |
Color Diagnostics, |
RCV000567017 | SCV001346623 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-11 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with leucine at codon 28 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 2/239990 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. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003478110 | SCV004222061 | uncertain significance | not provided | 2022-11-18 | criteria provided, single submitter | clinical testing | The variant has not been reported in the published literature. The frequency of this variant in the general population, 0.0000083 (2/239990 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |
All of Us Research Program, |
RCV004003705 | SCV004832355 | uncertain significance | Lynch syndrome | 2024-01-11 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with leucine at codon 28 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 hereditary cancer in the literature. This variant has been identified in 2/239990 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. |