Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001012435 | SCV001172884 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-12-02 | criteria provided, single submitter | clinical testing | The c.1618delA pathogenic mutation, located in coding exon 10 of the MSH2 gene, results from a deletion of one nucleotide at nucleotide position 1618, causing a translational frameshift with a predicted alternate stop codon (p.S540Vfs*3). This mutation has been detected in individuals with hereditary non-polyposis colorectal cancer (HNPCC)/Lynch syndrome, with at least one meeting Amsterdam criteria whose tumor demonstrated loss of MSH2 and MSH6 staining on immunohistochemistry (IHC) (Clarke EV et al. Fam Cancer, 2019 07;18:317-325; Ambry internal data). 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. |
Invitae | RCV001384789 | SCV001584436 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2023-06-22 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 819674). This premature translational stop signal has been observed in individual(s) with Lynch syndrome (PMID: 30729418). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser540Valfs*3) 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, |
RCV003455075 | SCV004186824 | 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. |