ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.37C>T (p.Pro13Ser) (rs1060501208)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000468196 SCV000545355 uncertain significance Li-Fraumeni syndrome 2018-08-08 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 13 of the TP53 protein (p.Pro13Ser). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and serine. 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. ClinVar contains an entry for this variant (Variation ID: 406604). Experimental studies have shown that this variant does not affect transactivational activity of the TP53 protein in yeast-based assays (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.
GeneDx RCV000478642 SCV000567854 uncertain significance not provided 2018-09-11 criteria provided, single submitter clinical testing This variant is denoted TP53 c.37C>T at the cDNA level, p.Pro13Ser (P13S) at the protein level, and results in the change of a Proline to a Serine (CCT>TCT). This variant has been observed as a somatic variant in a cutaneous squamous cell carcinoma metastasis specimen (Li 2015). This variant is reported as having functional transactivation in the International Agency for Research on Cancer TP53 database based on functional assays by Kato et al. (2003). TP53 Pro13Ser was not observed at a significant allele frequency in large population cohorts (Lek 2016). Since Proline and Serine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. TP53 Pro13Ser is located in the transactivation domain and in a nuclear export signal (Pessoa 2014, Bode 2004, Zhang 2001). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available information, it is unclear whether TP53 Pro13Ser is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000574176 SCV000667186 uncertain significance Hereditary cancer-predisposing syndrome 2017-01-10 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence

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