ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.534C>A (p.His178Gln) (rs1555526001)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000698003 SCV000826641 uncertain significance Li-Fraumeni syndrome 2018-10-16 criteria provided, single submitter clinical testing This sequence change replaces histidine with glutamine at codon 178 of the TP53 protein (p.His178Gln). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TP53-related disease. However, a different variant (c.534C>G) giving rise to the same protein effect observed here (p.His178Gln) has been reported in an individual affected with anaplastic rhabdomyosarcoma (PMID: 24382691). ClinVar contains an entry for this variant (Variation ID: 575702). An experimental study in yeast has shown that this variant impairs the transcriptional transactivation activity of the TP53 protein (PMID: 12826609). A different missense substitution at this codon (p.His178Asp) has been determined to be pathogenic (PMID: 21345075, 26094658, 12826609, 22829111). This suggests that the histidine residue is critical for TP53 protein function and that other missense substitutions at this position may also be pathogenic. 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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