Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000490870 | SCV000580379 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-12-03 | criteria provided, single submitter | clinical testing | The c.1128_1132delAAAGA pathogenic mutation, located in coding exon 4 of the MSH6 gene, results from a deletion of 5 nucleotides at nucleotide positions 1128 to 1132, causing a translational frameshift with a predicted alternate stop codon (p.R379*). A similar alteration (c.1135_1139del) resulting in the same stop codon was reported in a patient diagnosed at age 38 with both ovarian cancer and MSI-H endometrial cancer with absent MSH6 expression by immunohistochemistry analysis (Kets CM et al. Br. J. Cancer 2006 Dec;95:1678-82; Overbeek LI et al. Br. J. Cancer 2007 May;96:1605-12). 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000586921 | SCV000695775 | likely pathogenic | Lynch syndrome | 2015-12-07 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001851343 | SCV002184902 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2023-12-05 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg379*) 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: 428442). For these reasons, this variant has been classified as Pathogenic. |
Myriad Genetics, |
RCV003449336 | SCV004188286 | pathogenic | Lynch syndrome 5 | 2023-08-11 | 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. |