ClinVar Miner

Submissions for variant NM_000546.6(TP53):c.463A>G (p.Thr155Ala)

gnomAD frequency: 0.00001  dbSNP: rs772683278
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000534841 SCV000629821 uncertain significance Li-Fraumeni syndrome 2023-08-17 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with TP53-related conditions. This variant is present in population databases (rs772683278, gnomAD 0.007%). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 155 of the TP53 protein (p.Thr155Ala). 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. Experimental studies have shown that this missense change does not substantially affect TP53 function (PMID: 12826609, 22046250). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 12826609, 29979965, 30224644) indicates that this missense variant is not expected to disrupt TP53 function. ClinVar contains an entry for this variant (Variation ID: 458544).
GeneDx RCV001563388 SCV001786319 uncertain significance not provided 2020-01-02 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Published functional studies demonstrate functional transactivation and retained growth suppression activities (Kato 2003, Bernard 2011, Kotler 2018, Giacomelli 2018); This variant is associated with the following publications: (PMID: 30224644, 12826609, 29979965, 28176830, 22046250, 27070704, 25801821, 24665023, 24729566, 26205736, 23845441, 19139070, 18415037, 25496518, 17903248, 1868473)
Genome-Nilou Lab RCV002289733 SCV002582074 uncertain significance Hereditary cancer-predisposing syndrome 2022-06-18 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002289732 SCV002582637 uncertain significance Li-Fraumeni syndrome 1 2022-06-18 criteria provided, single submitter clinical testing
Ambry Genetics RCV002289733 SCV002639880 likely benign Hereditary cancer-predisposing syndrome 2020-10-30 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.

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