ClinVar Miner

Submissions for variant NM_003722.5(TP63):c.1807G>C (p.Asp603His)

gnomAD frequency: 0.00003  dbSNP: rs767906723
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001982230 SCV002214305 uncertain significance TP63-Related Spectrum Disorders 2023-12-04 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 603 of the TP63 protein (p.Asp603His). This variant is present in population databases (rs767906723, gnomAD 0.06%). This missense change has been observed in individual(s) with cleft lip and palate (PMID: 16740912). This variant is also known as 1690G>C D564H. ClinVar contains an entry for this variant (Variation ID: 1433359). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TP63 protein function with a positive predictive value of 80%. 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.
Fulgent Genetics, Fulgent Genetics RCV002484647 SCV002778477 uncertain significance ADULT syndrome; Ankyloblepharon-ectodermal defects-cleft lip/palate syndrome; Ectrodactyly, ectodermal dysplasia, and cleft lip-palate syndrome 3; Limb-mammary syndrome; Rapp-Hodgkin syndrome; Split hand-foot malformation 4; Orofacial cleft 8 2021-09-03 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004746523 SCV005350346 uncertain significance TP63-related disorder 2024-05-21 no assertion criteria provided clinical testing The TP63 c.1807G>C variant is predicted to result in the amino acid substitution p.Asp603His. This variant has been reported in an individual with bilateral complete cleft lip and palate, inherited from her clinically unaffected father (Leoyklang et al. 2006. PubMed ID: 16740912). This variant is reported in 0.060% of alleles in individuals of East Asian descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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