Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000806058 | SCV000946038 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2024-09-03 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Cys765*) in the MSH6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 18269114, 24362816). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MSH6-related conditions. ClinVar contains an entry for this variant (Variation ID: 650829). For these reasons, this variant has been classified as Pathogenic. |
| Color Diagnostics, |
RCV001184647 | SCV001350674 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-08-07 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 4 of the MSH6 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of MSH6 function is a known mechanism of disease. Based on available evidence, this variant is classified as Pathogenic. |
| Ambry Genetics | RCV001184647 | SCV003867473 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-01-24 | criteria provided, single submitter | clinical testing | The p.C765* pathogenic mutation (also known as c.2295C>A), located in coding exon 4 of the MSH6 gene, results from a C to A substitution at nucleotide position 2295. This changes the amino acid from a cysteine to a stop codon within coding exon 4. This alteration has been identified in a Thai endometrial cancer cohort (Manchana T et al. Asian Pac J Cancer Prev, 2021 May;22:1477-1483). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Myriad Genetics, |
RCV003453682 | SCV004189658 | pathogenic | Lynch syndrome 5 | 2023-11-14 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. |
| Revvity Omics, |
RCV003489898 | SCV004238292 | likely pathogenic | not provided | 2023-02-03 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV004569629 | SCV005054854 | pathogenic | Endometrial carcinoma | 2024-03-12 | criteria provided, single submitter | clinical testing |