Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV000581390 | SCV000690238 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-05 | criteria provided, single submitter | clinical testing | This missense variant replaces methionine with threonine at codon 654 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 1/251186 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. |
| Invitae | RCV001860090 | SCV002135739 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2023-10-13 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000581390 | SCV002720127 | likely benign | Hereditary cancer-predisposing syndrome | 2023-11-21 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Prevention |
RCV004530630 | SCV004118062 | uncertain significance | MSH6-related disorder | 2023-06-06 | criteria provided, single submitter | clinical testing | The MSH6 c.1961T>C variant is predicted to result in the amino acid substitution p.Met654Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-48027083-T-C), and has been interpreted as uncertain in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/491889/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
| All of Us Research Program, |
RCV004002345 | SCV004838181 | uncertain significance | Lynch syndrome | 2023-10-02 | criteria provided, single submitter | clinical testing |