ClinVar Miner

Submissions for variant NM_003722.5(TP63):c.740A>G (p.His247Arg)

dbSNP: rs864621968
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Programa de Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília RCV000206266 SCV000223904 pathogenic Ectrodactyly, ectodermal dysplasia, and cleft lip-palate syndrome 3 2015-04-01 criteria provided, single submitter research
GeneDx RCV000312203 SCV000329555 pathogenic not provided 2024-05-09 criteria provided, single submitter clinical testing Reported in two unrelated individuals with Ectrodactyly-Ectodermal dysplasia-Clefting (EEC) syndrome in published literature (PMID: 19903181); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as p.His208Arg; This variant is associated with the following publications: (PMID: 29620206, 32881366, 37665243, 26380986, 12037717, 21464285, 21652629, 17224651, 19903181)
Labcorp Genetics (formerly Invitae), Labcorp RCV000821003 SCV000961742 pathogenic TP63-Related Spectrum Disorders 2022-03-27 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p. His247 amino acid residue in TP63. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16691622, 19663851). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 208163). This missense change has been observed in individual(s) with ectrodactyly–ectodermal dysplasia–cleft lip ⁄ palate (EEC) syndrome (PMID: 19903181, 26380986). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 247 of the TP63 protein (p.His247Arg).
Royal Medical Services, Bahrain Defence Force Hospital RCV005208129 SCV005686378 pathogenic Ankyloblepharon-ectodermal defects-cleft lip/palate syndrome criteria provided, single submitter clinical testing The TP63 variant c.740A>G p.(His247Arg) causes an amino acid change from His to Arg at position 247 in exon(s) no. 5 (of 14). According to HGMD Professional 2024.2, this variant has previously been described as disease causing for EEC syndrome (PMID:19903181, 32881366). ClinVar lists this variant (Interpretation: Pathogenic; Variation ID: 208163; Accession: VCV000208163.10).

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