Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000215698 | SCV000279142 | uncertain significance | not specified | 2016-02-23 | criteria provided, single submitter | clinical testing | This variant is denoted PMS2 c.1556_1559delATGCinsGTGT at the cDNA level and p.Tyr519_Ala520delinsCysVal (Y519_A520delinsCV) at the protein level. The normal sequence, with the bases that are deleted in braces and inserted in brackets, is GAGT{ATGC}[GTGT]GGCC.The deletion and insertion results in the replacement of the two residues, Tyrosine and Alanine, with Cysteine and Valine, creating two adjacent missense changes: Tyr519Cys and Ala520Val.Both variants were reported in an individual with a personal history of a Lynch syndrome-related cancer and/or polyps who also harbored a pathogenic MSH2 variant (Yurgelun 2015).However, the authors did not clarify whether the two PMS2 variants were on the same or opposite chromosomes (in cis or trans).When studied independently, PMS2 Tyr519Cys was found to retain mismatch repair activity in an in vitro assay (Drost 2013).PMS2 Ala520Val has not, to our knowledge, been reported independent of PMS2 Tyr519Cys. |