ClinVar Miner

Submissions for variant NM_000546.6(TP53):c.903A>G (p.Pro301=) (rs72661120)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163363 SCV000213900 likely benign Hereditary cancer-predisposing syndrome 2014-08-28 criteria provided, single submitter clinical testing This alteration is classified as likely 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.
GeneDx RCV000436196 SCV000517836 likely benign not specified 2017-10-04 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.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000436196 SCV000540571 likely benign not specified 2016-03-28 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ExAC: 0.2% (31/16512) South Asian; ClinVar: 1 LB
Invitae RCV001081862 SCV000557356 benign Li-Fraumeni syndrome 2020-11-21 criteria provided, single submitter clinical testing
Color Health, Inc RCV000163363 SCV000686780 likely benign Hereditary cancer-predisposing syndrome 2016-10-07 criteria provided, single submitter clinical testing
Institute for Biomarker Research,Medical Diagnostic Laboratories, L.L.C. RCV000163363 SCV000803172 likely benign Hereditary cancer-predisposing syndrome 2018-05-23 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000760104 SCV000889886 benign not provided 2017-12-20 criteria provided, single submitter clinical testing
Institute of Biochemistry, Molecular Biology and Biotechnology,University of Colombo RCV001270284 SCV001450504 likely benign Familial cancer of breast criteria provided, single submitter case-control
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001355179 SCV001549984 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The TP53 p.Pro301= variant was identified in 7 of 364 proband chromosomes (frequency: 0.02) from Indian individuals or families with breast cancer and was not identified in 372 control chromosomes from healthy individuals (Damineni 2014). The variant was also identified in dbSNP (ID: rs72661120 as “With Likely benign allele”) and ClinVar (classified as likely benign by Ambry Genetics, GeneDx, LMM, Color Genomics and Institute for Biomarker Research and as benign by Invitae). The variant was not identified in GeneInsight-COGR, LOVD 3.0, or IARC TP53 Database. The variant was identified in control databases in 69 of 246266 chromosomes at a frequency of 0.0003 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: South Asian in 65 of 30782 chromosomes (freq: 0.002), African in 1 of 15304 chromosomes (freq: 0.00007), Other in 1 of 5486 chromosomes (freq: 0.0002), and European Non-Finnish in 2 of 111720 chromosomes (freq: 0.00002), while it was not observed in the Latino, Ashkenazi Jewish, East Asian or Finnish populations. The p.Pro301= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. The variant occurs outside of the splicing consensus sequence and only 1 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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