Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000486454 | SCV000567118 | uncertain significance | not provided | 2015-07-09 | criteria provided, single submitter | clinical testing | This variant is denoted MSH2 c.2636A>C at the cDNA level, p.Gln879Pro (Q879P) at the protein level, and results in the change of a Glutamine to a Proline (CAA>CCA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MSH2 Gln879Pro 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 Glutamine and Proline differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. MSH2 Gln879Pro occurs at a position that is conserved in mammals and is located in the helix-turn-helix domain (Lutzen 2008). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether MSH2 Gln879Pro is pathogenic or benign. We consider it to be a variant of uncertain significance. |