Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001181884 | SCV001347129 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2020-01-15 | criteria provided, single submitter | clinical testing | This variant inserts 2 nucleotides in exon 10 of the MSH6 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been identified in 1/234966 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of MSH6 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Likely Pathogenic. |
| Gene |
RCV001779129 | SCV002015621 | uncertain significance | not provided | 2021-05-11 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek 2016); Frameshift variant predicted to result in protein truncation as the last 24 amino acids are replaced with 9 different amino acids, although loss-of-function variants have not been reported downstream of this position in the protein; Lost residues are located in the critical binding site of MSH2 of the ATPase domain (Kariola 2002, Warren 2007, Kansikas 2011); This variant is associated with the following publications: (PMID: 29922827) |
| Invitae | RCV003769995 | SCV004655486 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2023-07-05 | criteria provided, single submitter | clinical testing | Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 922038). This variant has not been reported in the literature in individuals affected with MSH6-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Cys1337Phefs*10) in the MSH6 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 24 amino acid(s) of the MSH6 protein. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |