Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000559986 | SCV000625277 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2021-03-10 | criteria provided, single submitter | clinical testing | This variant has been observed in a family affected with Lynch syndrome (PMID: 27601186). ClinVar contains an entry for this variant (Variation ID:455503). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Pro507Leufs*19) in the MSH2 gene. It is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). |
| Laboratory for Molecular Medicine, |
RCV000604643 | SCV000712560 | pathogenic | Lynch syndrome | 2016-11-09 | criteria provided, single submitter | clinical testing | The p.Pro507fs variant in MSH2 has not been previously reported in individuals w ith Lynch Syndrome and was absent from large population studies, though the abil ity of these studies to accurately detect indels may be limited. This variant is predicted to cause a frameshift, which alters the protein?s amino acid sequence beginning at position 507 and leads to a premature termination codon 19 amino a cids downstream. This alteration is then predicted to lead to a truncated or abs ent protein. Heterozygous loss of function of the MSH2 gene is an established di sease mechanism in Lynch Syndrome. In summary, the available evidence suggests t hat this variant is pathogenic for Lynch Syndrome in an autosomal dominant manne r based upon the predicted impact to the protein. |
| Ambry Genetics | RCV002395283 | SCV002709600 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-08-30 | criteria provided, single submitter | clinical testing | The c.1520delC pathogenic mutation, located in coding exon 10 of the MSH2 gene, results from a deletion of one nucleotide at nucleotide position 1520, causing a translational frameshift with a predicted alternate stop codon (p.P507Lfs*19). This alteration has been identified in a cohort of Swedish Lynch syndrome families (Lagerstedt-Robinson K et al. Oncol. Rep. 2016 Nov;36:2823-2835). 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. |
| Myriad Genetics, |
RCV003449534 | SCV004188177 | pathogenic | Lynch syndrome 1 | 2023-08-02 | 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 | RCV003449534 | SCV004196853 | pathogenic | Lynch syndrome 1 | 2023-05-05 | criteria provided, single submitter | clinical testing |