ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.354A>T (p.Thr118=) (rs751978853)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163547 SCV000214105 likely benign Hereditary cancer-predisposing syndrome 2015-06-01 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.
Invitae RCV000225831 SCV000285190 likely benign Li-Fraumeni syndrome 2020-12-07 criteria provided, single submitter clinical testing
GeneDx RCV000421071 SCV000514936 benign not specified 2015-07-16 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000421071 SCV000602267 likely benign not specified 2017-01-19 criteria provided, single submitter clinical testing
Color Health, Inc RCV000163547 SCV000911992 likely benign Hereditary cancer-predisposing syndrome 2017-11-25 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000421071 SCV000920319 likely benign not specified 2018-07-02 criteria provided, single submitter clinical testing Variant summary: TP53 c.354A>T 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 5.7e-05 in 245848 control chromosomes (gnomAD). The observed variant frequency is approximately 1.43 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 benign. To our knowledge, no occurrence of c.354A>T in individuals affected with Li-Fraumeni Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Four ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Mendelics RCV000989724 SCV001140267 likely benign Squamous cell carcinoma of the head and neck 2019-05-28 criteria provided, single submitter clinical testing

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