Submissions for variant NM_003722.5(TP63):c.1054A>G (p.Arg352Gly)

dbSNP: rs121908847

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Servicio Canario de Salud, Hospital Universitario Nuestra Sra. de Candelaria	RCV002467435	SCV002758773	uncertain significance	Ectrodactyly, ectodermal dysplasia, and cleft lip-palate syndrome 3	2022-05-08	criteria provided, single submitter	clinical testing	The c.1054A>G (p.Arg352Gly) TP63 variant has been reported in our laboratory in a 41-year-old woman with diagnosis of ectrodactyly and asymptomatic parents. Patient with two previous legal abortions due to fetuses affected by ectrodactyly, in one of them the presence of this heterozygous variant could be confirmed. It has been previously reported in non-syndromic cleft lip (PMID 16740912). This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 6547). In silico analysis (CADD, Mutation Taster, SIFT, PolyPhen2) supports that this missense variant has a deleterious effect on protein structure/function. To date there are no functional/experimental studies that evaluate the impact on protein. In summary, c.1054A>G (p.Arg352Gly) TP63 variant meets our criteria to be classified as Variant of Uncertain Significance-Probably Pathogenic based upon its absence from controls, computational evidence of pathogenicity and and the clinical correlation in this family´s phenotype.
OMIM	RCV000006922	SCV000027118	pathogenic	Orofacial cleft 8	2006-06-01	no assertion criteria provided	literature only