Total submissions: 8
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| International Society for Gastrointestinal Hereditary Tumours |
RCV000074696 | SCV000107901 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
| Invitae | RCV000524125 | SCV000551072 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2023-11-28 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu634*) 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 premature translational stop signal has been observed in individual(s) with endometrial cancer and other Lynch syndrome-associated cancers (PMID: 12732731, 15098177). ClinVar contains an entry for this variant (Variation ID: 89232). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV001013617 | SCV001174225 | pathogenic | Hereditary cancer-predisposing syndrome | 2024-02-01 | criteria provided, single submitter | clinical testing | The c.1901_1902delTG pathogenic mutation, located in coding exon 4 of the MSH6 gene, results from a deletion of two nucleotides at nucleotide positions 1901 to 1902, causing a translational frameshift with a predicted alternate stop codon (p.L634*). This mutation has been reported in a proband with MSI-high endometrial cancer diagnosed at age 58 (Goodfellow PJ et al. Proc. Natl. Acad. Sci. U.S.A., 2003 May;100:5908-13). 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001284179 | SCV001469820 | pathogenic | not provided | 2020-01-03 | criteria provided, single submitter | clinical testing | The variant creates a premature stop codon, and is therefore predicted to result in the loss of a functional protein. Found in at least one patient with expected phenotype for this gene, and not found in general population data. Segregation with disease in affected individuals from a single family. |
| Gene |
RCV001284179 | SCV001778281 | pathogenic | not provided | 2020-11-10 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Observed in patients with Lynch-related cancers (Goodfellow 2003); This variant is associated with the following publications: (PMID: 12732731) |
| Myriad Genetics, |
RCV003450935 | SCV004185580 | pathogenic | Lynch syndrome 5 | 2023-08-16 | 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. |
| Baylor Genetics | RCV003466937 | SCV004195830 | likely pathogenic | Endometrial carcinoma | 2023-02-22 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV001284179 | SCV001549372 | uncertain significance | not provided | no assertion criteria provided | clinical testing |