Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000215974 | SCV000279144 | uncertain significance | not specified | 2016-01-26 | criteria provided, single submitter | clinical testing | This variant is denoted PMS2 c.1688_1689delGAinsAG at the cDNA level and p.Arg563Gln (R563Q) at the protein level.The normal sequence, with the bases that are deleted in braces and inserted in brackets, is TTTC{GA}[AG]GTTT.This in frame deletion and insertion results in the missense change of an Arginine to a Glutamine (CGA>CAG).PMS2 Arg563Gln, due to the missense substitution c.1688G>A, has been observed in tissue of 7/20 breast cancers but was absent in the normal adjacent breast tissue (Balogh 2006).PMS2 Arg563Gln was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.Since Arginine and Glutamine differ in some properties, this is considered a semi-conservative amino acid substitution.PMS2 Arg563Gln occurs at a position that is not conserved across species and is not located in a known functional domain (Guarne 2001, Fukui 2011).In addition, in silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available information, we consider PMS2 Arg563Gln to be a variant of uncertain significance. |