Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| International Society for Gastrointestinal Hereditary Tumours |
RCV000076745 | SCV000107782 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
| Ambry Genetics | RCV000491733 | SCV000580621 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-01-29 | criteria provided, single submitter | clinical testing | The c.898_899dupAT pathogenic mutation, located in coding exon 5 of the MSH2 gene, results from a duplication of AT at nucleotide position 898, causing a translational frameshift with a predicted alternate stop codon (p.M300Ifs*2). This mutation (designated as c.898_899insAT) has been reported in an HNPCC/Lynch syndrome family from Northern China meeting original Bethesda guidelines (Sheng JQ et al. Chin J Dig Dis, 2006;7:197-205). This mutation was also identified in an individual with endometrioid/clear cell endometrial cancer diagnosed at age 44 whose tumor indicated loss of MSH2 and MSH6 protein expression in a cohort of 198 Chinese endometrial cancer patients (Tian W et al. Int. J. Cancer, 2019 09;145:1290-1298). In addition to the clinical data presented in the literature, his 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. |
| Invitae | RCV002514360 | SCV003524759 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2021-11-24 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with endometrial cancer (PMID: 31054147). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Met300Ilefs*2) in the MSH2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). |
| Myriad Genetics, |
RCV003452973 | SCV004187024 | pathogenic | Lynch syndrome 1 | 2023-07-28 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |
| Baylor Genetics | RCV003452973 | SCV004196908 | pathogenic | Lynch syndrome 1 | 2022-05-09 | criteria provided, single submitter | clinical testing |