Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001192999 | SCV001361505 | uncertain significance | not specified | 2019-09-20 | criteria provided, single submitter | clinical testing | Variant summary: POLE c.1306C>T (p.Pro436Ser) results in a non-conservative amino acid change located in the exonuclease (proofreading) domain (Spier_2015). Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251188 control chromosomes (gnomAD). The variant, c.1306C>T, has been reported as a de novo variant in one individual affected with attenuated polyposis and colorectal cancer (Spier_2015). These data indicate that the variant maybe associated with the disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |