Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000076483 | SCV000107512 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation introducing premature termination codon |
Color Diagnostics, |
RCV000580315 | SCV000685048 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-04-02 | criteria provided, single submitter | clinical testing | This variant deletes 2 nucleotides in exon 15 of the MSH2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in an individual affected with colorectal cancer (PMID: 15365996). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of MSH2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |
Institute of Human Genetics, |
RCV001723649 | SCV001950063 | pathogenic | Lynch syndrome 1 | 2021-07-12 | criteria provided, single submitter | clinical testing | The variant was identified in a man with CRC at the age of 29 and ICH loss of MSH2/MSH6 |
Invitae | RCV001854329 | SCV002245877 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2021-11-07 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Cys822*) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with personal and family history consistent with Lynch syndrome (PMID: 15365996). ClinVar contains an entry for this variant (Variation ID: 90981). For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV000580315 | SCV002732336 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-02-01 | criteria provided, single submitter | clinical testing | The c.2466_2467delTG pathogenic mutation, located in coding exon 15 of the MSH2 gene, results from a deletion of two nucleotides at nucleotide positions 2466 to 2467, causing a translational frameshift with a predicted alternate stop codon (p.C822*). This mutation, designated also as p.C822X, was detected in an individual with MSH2-/MSI-H coecal cancer (Krüger S et al. Hum. Mutat. 2004 Oct;24:351-2). 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. |
Gene |
RCV003159096 | SCV003853204 | pathogenic | not provided | 2022-10-03 | 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 at significant frequency in large population cohorts (gnomAD); Observed in an individual with a personal and family history consistent with pathogenic variants in this gene (Krger et al., 2004); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; This variant is associated with the following publications: (PMID: 15365996) |
Myriad Genetics, |
RCV001723649 | SCV004188022 | pathogenic | Lynch syndrome 1 | 2023-08-08 | 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. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003159096 | SCV004220985 | pathogenic | not provided | 2023-08-18 | criteria provided, single submitter | clinical testing | The MSH2 c.2466_2467del (p.Cys822*) variant causes the premature termination of MSH2 protein synthesis. In the published literature, this variant has been reported in a family with Lynch syndrome (PMID: 15365996 (2004)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Based on the available information, this variant is classified as pathogenic. |