Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000130192 | SCV000185029 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-01-15 | criteria provided, single submitter | clinical testing | The c.3198_3199delTA pathogenic mutation, located in coding exon 5 of the MSH6 gene, results from a deletion of two nucleotides at nucleotide positions 3198 to 3199, causing a translational frameshift with a predicted alternate stop codon (p.Y1066*). This alteration has been identified in an individual undergoing multi-gene panel testing for a personal and/or family history of cancer (Espenschied CR et al. J Clin Oncol, 2017 Aug;35:2568-2575). 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. |
| Labcorp Genetics |
RCV000540383 | SCV000624830 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2023-07-17 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Tyr1066*) 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: 141603). |
| Gene |
RCV001588984 | SCV001822315 | pathogenic | not provided | 2020-12-28 | 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 2016); Truncated variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Observed in individuals referred for multi-gene panel testing (LaDuca 2017); This variant is associated with the following publications: (PMID: 28152038) |
| Myriad Genetics, |
RCV003453072 | SCV004188329 | pathogenic | Lynch syndrome 5 | 2023-08-22 | 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 | RCV003467133 | SCV004196343 | likely pathogenic | Endometrial carcinoma | 2021-12-18 | criteria provided, single submitter | clinical testing |