Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000226045 | SCV000289369 | benign | not provided | 2016-03-04 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000256131 | SCV000322483 | likely benign | not specified | 2018-03-13 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000256131 | SCV000602042 | uncertain significance | not specified | 2017-01-12 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV000256131 | SCV000806774 | benign | not specified | 2017-10-13 | criteria provided, single submitter | clinical testing | |
Integrated Genetics/Laboratory Corporation of America | RCV000256131 | SCV000918086 | benign | not specified | 2018-07-13 | criteria provided, single submitter | clinical testing | Variant summary: POLE c.4184A>G (p.Tyr1395Cys) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00074 in 277082 control chromosomes in the gnomAD database, including 1 homozygotes. The observed variant frequency is approximately 52-fold of the estimated maximal expected allele frequency for a pathogenic variant in POLE causing Colorectal Cancer phenotype (1.4e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.4184A>G in individuals affected with Colorectal Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (2x likely benign/benign, 1x VUS). Based on the evidence outlined above, the variant was classified as benign. |