ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.31G>A (p.Glu11Lys) (rs201382018)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000485338 SCV000565944 uncertain significance not specified 2017-05-09 criteria provided, single submitter clinical testing This variant is denoted TP53 c.31G>A at the cDNA level, p.Glu11Lys (E11K) at the protein level, and results in the change of a Glutamic Acid to a Lysine (GAG>AAG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. TP53 Glu11Lys was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Glutamic Acid and Lysine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. TP53 Glu11Lys occurs at a position that is not conserved across species and is located within the region of interaction with HRMT1L2 (UniProt). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether TP53 Glu11Lys is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000548671 SCV000629802 uncertain significance Li-Fraumeni syndrome 2018-08-31 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 11 of the TP53 protein (p.Glu11Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs201382018, ExAC 0.002%). This variant has not been reported in the literature in individuals with TP53-related disease. ClinVar contains an entry for this variant (Variation ID: 418693). Experimental studies have shown that this missense change does not alter TP53 protein binding to RPA or transcriptional transactivation activity (PMID: 920706, 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.
Ambry Genetics RCV000563270 SCV000672374 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-02 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Counsyl RCV000663228 SCV000786429 uncertain significance Li-Fraumeni syndrome 1 2018-05-01 criteria provided, single submitter clinical testing
Color RCV000563270 SCV000905144 likely benign Hereditary cancer-predisposing syndrome 2015-10-19 criteria provided, single submitter clinical testing

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