Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000816938 | SCV000957467 | uncertain significance | TP63-Related Spectrum Disorders | 2018-08-15 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with alanine at codon 348 of the TP63 protein (p.Pro348Ala). The proline residue is highly conserved and there is a small physicochemical difference between proline and alanine. This variant is not present in population databases (ExAC no frequency). 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. The observation of one or more missense substitutions at this codon (p.Pro349Ser) in affected individuals suggests that this may be a clinically significant residue (PMID: 11462173). 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: "Benign"; Align-GVGD: "Class C25"). This variant has not been reported in the literature in individuals with TP63-related disease. |