Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000074781 | SCV000107991 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
Invitae | RCV001854279 | SCV002243237 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2021-09-16 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 89316). This premature translational stop signal has been observed in individual(s) with clinical features of Lynch syndrome (PMID: 18301448). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Thr924Aspfs*11) 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). |
Ambry Genetics | RCV002433572 | SCV002751934 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-08-17 | criteria provided, single submitter | clinical testing | The c.2768dupA pathogenic mutation, located in coding exon 4 of the MSH6 gene, results from a duplication of A at nucleotide position 2768, causing a translational frameshift with a predicted alternate stop codon (p.T924Dfs*11). This alteration, described as c.2768_2769insA, was identified in a patient with MSH6-deficient rectal cancer at age 30 (Steinke V et al. Eur. J. Hum. Genet. 2008 May;16:587-92). 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, |
RCV003450949 | SCV004187340 | pathogenic | Lynch syndrome 5 | 2023-08-18 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |