ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.666G>T (p.Pro222=) (rs72661118)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000162396 SCV000212719 benign Hereditary cancer-predisposing syndrome 2014-11-18 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae RCV001085434 SCV000253314 likely benign Li-Fraumeni syndrome 2020-11-20 criteria provided, single submitter clinical testing
Counsyl RCV000409816 SCV000489223 likely benign Li-Fraumeni syndrome 1 2016-09-06 criteria provided, single submitter clinical testing
Color Health, Inc RCV000162396 SCV000686759 likely benign Hereditary cancer-predisposing syndrome 2015-04-20 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000588456 SCV000697445 benign not provided 2017-07-21 criteria provided, single submitter clinical testing Variant summary: The TP53 c.666G>T (p.Pro222Pro) variant involves the alteration of a non-conserved nucleotide causing a synonymous change and 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may alter ESE binding. However, these predictions have yet to be confirmed by functional studies. This variant was found in 12/277398 control chromosomes, predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.000087 (11/126590). This frequency is about 2 times the estimated maximal expected allele frequency of a pathogenic TP53 variant (0.0000398), suggesting this is likely a benign polymorphism found primarily in population(s) of European (Non-Finnish) origin. Multiple publications have cited the variant as a somatic occurrence across varying cancers, however, germline analysis was not performed in these studies. A publication, Damineni_2014, does cite the variant, c.666G>C (p.Pro222Pro) as a germline occurrence in a BrC pt, however, limited information is provided (ie, no co-occurrence or cosegregation data and TP53 exons 5-9 were only assessed). In addition, multiple clinical diagnostic laboratories classified this variant as likely benign/benign. Taken together, this variant is classified as benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000588456 SCV001134875 likely benign not provided 2018-12-31 criteria provided, single submitter clinical testing
GeneDx RCV000588456 SCV001940211 benign not provided 2015-03-03 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 29979965)
Laboratory of Translational Genomics, National Cancer Institute RCV000119374 SCV000154281 not provided Neoplasm of ovary no assertion provided not provided

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.