Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003756675 | SCV004516122 | uncertain significance | TP63-Related Spectrum Disorders | 2024-01-11 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 408 of the TP63 protein (p.Arg408His). This variant is present in population databases (rs751698974, gnomAD 0.004%). This missense change has been observed in individual(s) with clinical features of TP63-related disorders (PMID: 30850703). 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. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on TP63 function (PMID: 30850703). 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, |
RCV005030227 | SCV005660629 | 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; Premature ovarian failure 21 | 2024-04-29 | criteria provided, single submitter | clinical testing |