Submissions for variant NM_000546.6(TP53):c.29T>G (p.Val10Gly)

dbSNP: rs1418778734

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV001017901	SCV001179065	uncertain significance	Hereditary cancer-predisposing syndrome	2019-01-25	criteria provided, single submitter	clinical testing	The p.V10G variant (also known as c.29T>G), located in coding exon 1 of the TP53 gene, results from a T to G substitution at nucleotide position 29. The valine at codon 10 is replaced by glycine, an amino acid with dissimilar properties. This variant was shown to have transactivation capabilities similar to wild type in yeast based functional studies (Kato S et al. Proc. Natl. Acad. Sci. USA. 2003 Jul 8;100(14):8424-9). Studies conducted in human cell lines indicate this alteration remains proficient at growth suppression (Giacomelli AO et al. Nat. Genet. 2018 Oct;50:1381-1387). This amino acid position is poorly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae	RCV001233678	SCV001406283	uncertain significance	Li-Fraumeni syndrome	2022-01-27	criteria provided, single submitter	clinical testing	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. Experimental studies have shown that this missense change does not substantially affect TP53 function (PMID: 12826609, 30224644). Advanced modeling of experimental studies (such as gene expression, population dynamics, functional pathways, and cell-cycle effects in cell culture) performed at Invitae indicates that this missense variant is not expected to disrupt TP53 protein function. ClinVar contains an entry for this variant (Variation ID: 822501). This missense change has been observed in individual(s) with breast cancer (PMID: 29522266, 33245408). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces valine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 10 of the TP53 protein (p.Val10Gly).
Genome-Nilou Lab	RCV001017901	SCV002582182	uncertain significance	Hereditary cancer-predisposing syndrome	2022-06-18	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002290536	SCV002582745	uncertain significance	Li-Fraumeni syndrome 1	2022-06-18	criteria provided, single submitter	clinical testing