Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| International Society for Gastrointestinal Hereditary Tumours |
RCV000076878 | SCV000108371 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
| Ambry Genetics | RCV002354272 | SCV002650436 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-10-17 | criteria provided, single submitter | clinical testing | The c.593dupT pathogenic mutation, located in coding exon 6 of the PMS2 gene, results from a duplication of T at nucleotide position 593, causing a translational frameshift with a predicted alternate stop codon (p.R199Pfs*50). This variant (described as c.592_593insT) has been identified in a proband who met Amsterdam I criteria for Lynch syndrome and tumor demonstrated high microsatellite instability with deficient PMS2 expression by immunohistochemistry (Woods MO et al. Gut, 2010 Oct;59:1369-77). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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 |
RCV003229807 | SCV003927312 | pathogenic | not provided | 2022-11-29 | criteria provided, single submitter | clinical testing | Frameshift 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); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Observed in an individual with colon cancer (Senter et al., 2008); This variant is associated with the following publications: (PMID: 26147798, 18602922) |