Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001342203 | SCV001536117 | uncertain significance | TP63-Related Spectrum Disorders | 2024-01-11 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 374 of the TP63 protein (p.Thr374Met). This variant is present in population databases (rs199807776, gnomAD 0.01%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with TP63-related conditions. ClinVar contains an entry for this variant (Variation ID: 1038841). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on TP63 protein function. 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, |
RCV002486385 | SCV002790329 | 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 ectodermal dysplasia syndrome; Split hand-foot malformation 4; Orofacial cleft 8 | 2022-03-17 | criteria provided, single submitter | clinical testing |