ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.214C>A (p.Pro72Thr) (rs587782769)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000223537 SCV000276961 likely benign Hereditary cancer-predisposing syndrome 2020-04-06 criteria provided, single submitter clinical testing In silico models in agreement (benign);Other data supporting benign classification
Invitae RCV001221060 SCV001393083 uncertain significance Li-Fraumeni syndrome 2020-10-22 criteria provided, single submitter clinical testing This sequence change replaces proline with threonine at codon 72 of the TP53 protein (p.Pro72Thr). The proline residue is weakly conserved and there is a small physicochemical difference between proline and threonine. This variant is present in population databases (rs587782769, ExAC 0.002%). This variant has not been reported in the literature in individuals with TP53-related conditions. ClinVar contains an entry for this variant (Variation ID: 232750). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color Health, Inc RCV000223537 SCV001736391 uncertain significance Hereditary cancer-predisposing syndrome 2021-02-01 criteria provided, single submitter clinical testing This missense variant replaces proline with threonine at codon 72 of the TP53 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/250672 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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