Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000167108 | SCV000217938 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-06-28 | criteria provided, single submitter | clinical testing | The p.G1072V variant (also known as c.3215G>T), located in coding exon 5 of the MSH6 gene, results from a G to T substitution at nucleotide position 3215. The glycine at codon 1072 is replaced by valine, 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 deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Gene |
RCV000213713 | SCV000279652 | uncertain significance | not provided | 2020-08-25 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Invitae | RCV000805949 | SCV000945925 | benign | Hereditary nonpolyposis colorectal neoplasms | 2023-08-14 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV003995558 | SCV004835653 | uncertain significance | Lynch syndrome | 2023-11-20 | criteria provided, single submitter | clinical testing | This missense variant replaces glycine with valine at codon 1072 of the MSH6 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 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 2/251364 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. |