Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000074960 | SCV000108175 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
Invitae | RCV001854286 | SCV002140049 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2021-01-10 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the MSH6 protein. Other variant(s) that disrupt this region (p.Leu1330Valfs*12) have been determined to be pathogenic (PMID: 2440087). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant has been observed in individual(s) with Lynch syndrome (PMID: 28528517). ClinVar contains an entry for this variant (Variation ID: 89492). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Phe1323Leufs*14) in the MSH6 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 38 amino acid(s) of the MSH6 protein. |