Submissions for variant NM_000546.6(TP53):c.409_417del (p.Leu137_Lys139del)

dbSNP: rs2073395622

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001213890	SCV001385543	pathogenic	Li-Fraumeni syndrome	2023-07-14	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the TP53 protein in which other variant(s) (p.Ala138Pro) have been determined to be pathogenic (PMID: 9569035, 12826609, 15548685, 17567834, 17606709, 19958544, 21343334). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 943654). 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 variant, c.409_417del, results in the deletion of 3 amino acid(s) of the TP53 protein (p.Leu137_Lys139del), but otherwise preserves the integrity of the reading frame.
Myriad Genetics, Inc.	RCV004033914	SCV004931898	likely pathogenic	Li-Fraumeni syndrome 1	2024-02-13	criteria provided, single submitter	clinical testing	This variant is considered likely pathogenic. Functional studies indicate this variant impacts protein function [PMID: 29979965]. This variant is expected to disrupt protein structure [Myriad internal data].