ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.319T>C (p.Tyr107His) (rs368771578)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen TP53 Variant Curation Expert Panel,ClinGen RCV000991146 SCV001142553 benign Li-Fraumeni syndrome 2019-08-28 reviewed by expert panel curation This variant has a minor allele frequency of 0.001122 (0.11%, 28/24,948 alleles) in the African subpopulation of the gnomAD cohort (BA1). The variant also has a BayesDel score < 0.16 and Align GVGD (Zebrafish) is Class C0 or Class C15 (BP4). Additionally, transactivation assays show partially functional variant according to Kato, et al. and there is no evidence of a dominant negative effect or loss of function according to Giacomelli, et al. (BS3_Supporting; PMID: 12826609, 30224644). Finally, this variant has been observed in at least 7 60+ year old females without a cancer diagnosis (BS2_Supporting; FLOSSIES database - https://whi.color.com). In summary, TP53 c.319T>C; p.Tyr107His meets criteria to be classified as benign for Li-Fraumeni syndrome. ACMG/AMP criteria applied, as specified by the TP53 Variant Curation Expert Panel: BA1, BP4, BS3_Supporting, BS2_Supporting.
Ambry Genetics RCV000128936 SCV000172807 likely benign Hereditary cancer-predisposing syndrome 2018-02-07 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other strong data supporting benign classification,In silico models in agreement (benign),Other data supporting benign classification
GeneDx RCV000235219 SCV000211739 likely benign not specified 2018-01-25 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.
Invitae RCV000588191 SCV000285186 likely benign not provided 2019-03-04 criteria provided, single submitter clinical testing
Counsyl RCV000411273 SCV000489333 uncertain significance Li-Fraumeni syndrome 1 2016-09-22 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000235219 SCV000597523 uncertain significance not specified 2017-05-30 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000588191 SCV000602266 likely benign not provided 2018-09-11 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000588191 SCV000697439 uncertain significance not provided 2017-08-09 criteria provided, single submitter clinical testing Variant summary: The TP53 c.319T>C (p.Tyr107His) variant involves the alteration of a conserved nucleotide. 3/5 in silico tools predict a benign outcome for this variant. This variant was found in 8/120968 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.000778 (8/10278). This frequency is about 20 times the estimated maximal expected allele frequency of a pathogenic TP53 variant (0.0000398), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. This variant has been reported in cancer patients without strong evidence for causality. In addition, multiple clinical diagnostic laboratories classified this variant as uncertain significance and one lab classified it as likely benign, all without evidence for independently evaluation. Taken together, this variant is classified as VUS-possibly benign until more evidence becomes available.
Color RCV000128936 SCV000910800 likely benign Hereditary cancer-predisposing syndrome 2016-03-09 criteria provided, single submitter clinical testing

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