ClinVar Miner

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

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Total submissions: 6
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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
Color RCV000162396 SCV000686759 likely benign Hereditary cancer-predisposing syndrome 2015-04-20 criteria provided, single submitter clinical testing
Counsyl RCV000409816 SCV000489223 likely benign Li-Fraumeni syndrome 1 2016-09-06 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America 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.
Invitae RCV000199198 SCV000253314 likely benign Li-Fraumeni syndrome 2017-12-30 criteria provided, single submitter clinical testing
Laboratory of Translational Genomics, National Cancer Institute RCV000119374 SCV000154281 not provided Neoplasm of ovary no assertion provided not provided

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