Submissions for variant NM_003722.5(TP63):c.1570G>A (p.Ala524Thr)

dbSNP: rs1403304957

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001971798	SCV002264139	uncertain significance	TP63-Related Spectrum Disorders	2021-08-10	criteria provided, single submitter	clinical testing	This variant is not present in population databases (ExAC no frequency). 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with TP63-related conditions. This sequence change replaces alanine with threonine at codon 524 of the TP63 protein (p.Ala524Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine.
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics	RCV002466729	SCV002761191	uncertain significance	ADULT syndrome	2022-11-24	criteria provided, single submitter	clinical testing	A heterozygous missense variation in exon 12 of the TP63 gene that results in the amino acid substitution of Threonine for Alanine at codon 524 (p.Ala524Thr) was detected. This variant has not been reported in the 1000 genomes and gnomAD databases. The reference codon is conserved across species. In summary, the variant meets our criteria to be classified as uncertain significance.