Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001390109 | SCV001591731 | pathogenic | TP63-Related Spectrum Disorders | 2020-10-10 | criteria provided, single submitter | clinical testing | This variant has been observed in individual(s) with ankyloblepharon–ectodermal dysplasia syndrome or TP63-related disorders (PMID: 17224651, Invitae). In at least one individual the variant was observed to be de novo. This variant is also known as Gly518Val. For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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"). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with valine at codon 557 of the TP63 protein (p.Gly557Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. |
| Laboratorio de Genetica e Diagnostico Molecular, |
RCV003136064 | SCV003806794 | likely pathogenic | ADULT syndrome | 2022-07-29 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PS4 supporting, PM1 moderated, PM2 moderated, PP3 supporting |