ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.885T>C (p.Pro295=) (rs200073907)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000161050 SCV000212943 likely benign Hereditary cancer-predisposing syndrome 2014-11-20 criteria provided, single submitter clinical testing
Color RCV000161050 SCV000537458 likely benign Hereditary cancer-predisposing syndrome 2015-07-24 criteria provided, single submitter clinical testing
Counsyl RCV000410106 SCV000488084 likely benign Li-Fraumeni syndrome 1 2015-12-22 criteria provided, single submitter clinical testing
GeneDx RCV000156005 SCV000211780 benign not specified 2014-07-25 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.
Integrated Genetics/Laboratory Corporation of America RCV000156005 SCV000920322 likely benign not specified 2018-08-14 criteria provided, single submitter clinical testing Variant summary: TP53 c.885T>C alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4.3e-05 in 277208 control chromosomes, predominantly at a frequency of 9.5e-05 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 2-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in TP53 causing Li-Fraumeni Syndrome phenotype (4e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. Though c.885T>C has been reported in the literature in a family with some family members affected with various cancer phenotypes (e.g. Gallo 1999), it was also reported in controls (de Andrade 2017). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as "likely benign." Based on the evidence outlined above, the variant was classified as likely benign.
Invitae RCV000119212 SCV000153954 likely benign Li-Fraumeni syndrome 2018-01-04 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000156005 SCV000205717 likely benign not specified 2013-08-15 criteria provided, single submitter clinical testing Pro295Pro in exon 8 of TP53: This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue and is not located withi n the splice consensus sequence. It has been identified in 1/1324 European chrom osomes by the ClinSeq project (dbSNP rs200073907). Pro295Pro in exon 8 of TP53: (allele frequency=1/1324; dbSNP rs200073907) **
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000156005 SCV000602282 likely benign not specified 2017-02-08 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000760103 SCV000889885 likely benign not provided 2018-08-14 criteria provided, single submitter clinical testing
True Health Diagnostics RCV000161050 SCV000805310 likely benign Hereditary cancer-predisposing syndrome 2018-03-16 no assertion criteria provided clinical testing

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