Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000076569 | SCV000107600 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
Clinical Genetics and Genomics, |
RCV001269636 | SCV001449761 | pathogenic | not provided | 2019-10-30 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001390797 | SCV001592644 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2020-03-23 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has been observed in individual(s) with Lynch syndrome (PMID: 17389002). ClinVar contains an entry for this variant (Variation ID: 91067). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Asp116Glyfs*57) in the MSH2 gene. It is expected to result in an absent or disrupted protein product. |
Ambry Genetics | RCV002453389 | SCV002613938 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-08-20 | criteria provided, single submitter | clinical testing | The c.347_350delATTG pathogenic mutation, located in coding exon 2 of the MSH2 gene, results from a deletion of 4 nucleotides at nucleotide positions 347 to 350, causing a translational frameshift with a predicted alternate stop codon (p.D116Gfs*57). This variant has been reported in an individual diagnosed with anaplastic astrocytoma exhibiting loss of MSH2 protein by immunohistochemistry at age 45 and with a family history of early onset colorectal cancer and kidney cancer (Lebrun C et al. Eur. J. Neurol., 2007 Apr;14:470-2). 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, |
RCV003452933 | SCV004188031 | pathogenic | Lynch syndrome 1 | 2023-07-26 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |