Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV004018331 | SCV004847956 | pathogenic | Lynch syndrome | 2015-07-30 | criteria provided, single submitter | clinical testing | The p.Ser113X variant in PMS2 has not been previously reported in individuals with Lynch syndrome and was absent from large population studies. This nonsense variant leads to a premature termination codon at position 113, which is predicted to lead to a truncated or absent protein. Heterozygous loss of function of the PMS2 gene is an established disease mechanism in Lynch syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1211/). In summary, this variant meets our criteria to be classified as pathogenic for Lynch syndrome (http://www.partners.org/personalizedmedicine/LMM) based upon predicted impact to the protein and absence in controls. |