ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.461G>A (p.Gly154Asp) (rs762846821)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000231149 SCV000285197 uncertain significance Li-Fraumeni syndrome 2015-12-25 criteria provided, single submitter clinical testing This sequence change replaces glycine with aspartic acid at codon 154 of the TP53 protein (p.Gly154Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is present in population databases (rs762846821, ExAC 0.002%) but has not been reported in the literature in the germline of individuals with a TP53-related disease. 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. In addition, the aspartic acid amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. In summary, this is a rare missense change that is not predicted to affect protein function or cause disease. However, the evidence is insufficient at this time to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000492535 SCV000581127 uncertain significance Hereditary cancer-predisposing syndrome 2016-07-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Conflicting evidence
Color RCV000492535 SCV000686740 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-08 criteria provided, single submitter clinical testing
Counsyl RCV000662397 SCV000784812 uncertain significance Li-Fraumeni syndrome 1 2017-01-03 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000764147 SCV000895132 uncertain significance Adrenocortical carcinoma, hereditary; Familial cancer of breast; Glioma susceptibility 1; Osteosarcoma; Li-Fraumeni syndrome 1; Nasopharyngeal carcinoma; Carcinoma of pancreas; Choroid plexus papilloma; Carcinoma of colon; Basal cell carcinoma, susceptibility to, 7; Hepatocellular carcinoma 2018-10-31 criteria provided, single submitter clinical testing

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