ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.1136G>A (p.Arg379His) (rs863224682)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000581851 SCV000691578 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-20 criteria provided, single submitter clinical testing
Counsyl RCV000410457 SCV000488737 uncertain significance Li-Fraumeni syndrome 1 2016-05-31 criteria provided, single submitter clinical testing
GeneDx RCV000235637 SCV000293685 uncertain significance not provided 2015-12-15 criteria provided, single submitter clinical testing This variant is denoted TP53 c.1136G>A at the cDNA level, p.Arg379His (R379H) at the protein level, and results in the change of an Arginine to a Histidine (CGC>CAC). This variant has been identified in at least one individual with early-onset colorectal cancer (Yurgelun 2015). TP53 Arg379His was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Arginine and Histidine share similar properties, this is considered a conservative amino acid substitution. TP53 Arg379His occurs at a position that is not conserved and is located in the region of interaction with CARM1 (UniProt). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether TP53 Arg379His is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000696782 SCV000825360 uncertain significance Li-Fraumeni syndrome 2018-12-16 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 379 of the TP53 protein (p.Arg379His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with colorectal cancer (PMID: 26086041). ClinVar contains an entry for this variant (Variation ID: 246221). An experimental study in yeast has shown that this variant does not impair the transcriptional transactivation activity of the TP53 protein (PMID: 12826609). 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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