Submissions for variant NM_000546.6(TP53):c.646G>C (p.Val216Leu)

dbSNP: rs730882025

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000466409	SCV000545343	uncertain significance	Li-Fraumeni syndrome	2022-08-04	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. 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 expected to disrupt TP53 protein function. ClinVar contains an entry for this variant (Variation ID: 406596). This variant has not been reported in the literature in individuals affected with TP53-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 216 of the TP53 protein (p.Val216Leu).
Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo	RCV001270272	SCV001450488	pathogenic	Squamous cell carcinoma of the head and neck		criteria provided, single submitter	case-control