ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.427G>A (p.Val143Met) (rs587782620)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
A.C.Camargo Cancer Center / LGBM, A.C.Camargo Cancer Center RCV000413546 SCV000492477 pathogenic Neoplasm of the breast criteria provided, single submitter research
Ambry Genetics RCV000132003 SCV000187062 uncertain significance Hereditary cancer-predisposing syndrome 2016-10-03 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Counsyl RCV000409072 SCV000489254 uncertain significance Li-Fraumeni syndrome 1 2016-09-09 criteria provided, single submitter clinical testing
Invitae RCV000227179 SCV000285196 uncertain significance Li-Fraumeni syndrome 2018-08-21 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 143 of the TP53 protein (p.Val143Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in an individual with breast cancer (PMID: 23469205). ClinVar contains an entry for this variant (Variation ID: 142657). Experimental studies report conflicting results for this variant. A study using yeast based transactivation assays classifies this variant as a non-functional allele which demonstrates loss of activity across 8 different promotors (PMID: 12826609). However, other studies in yeast have found that this variant demonstrates loss of transactivation activity for some promoters, while retaining activity for others (PMID: 9572492, 11222779). One of these studies also found that transactivation activity was retained for the 2 promoters tested in mammalian cells (PMID: 9572492). 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.

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