Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000413620 | SCV000490859 | pathogenic | not provided | 2016-10-05 | criteria provided, single submitter | clinical testing | The R266Q pathogenic variant in the TP63 gene, also referred to as R227Q due to the use of alternative nomenclature, is a common pathogenic variant that has been reported several times in association with Ectrodactyly-Ectodermal Dysplasia-Clefting (EEC) syndrome (van Bokhoven et al., 2001; Maclean et al., 2007; Sripathomsawat et al., 2011; Su et al., 2013). In vitro functional studies demonstrated that the R266Q variant enhances the transactivation of some TP63 targets and up-regulated the expression of mRNA and protein for TP63 target genes (Khokhar et al., 2008). The R266Q variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R266Q variant is a semi-conservative amino acid substitution, and occurs at a position that is conserved across species. We interpret R266Q as a pathogenic variant. |
Invitae | RCV001390108 | SCV001591730 | pathogenic | TP63-Related Spectrum Disorders | 2022-08-07 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on TP63 function (PMID: 18626511). 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 C35"). ClinVar contains an entry for this variant (Variation ID: 6550). This variant is also known as R227Q. This missense change has been observed in individual(s) with TP63-related conditions (PMID: 11462173). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 266 of the TP63 protein (p.Arg266Gln). |
MGZ Medical Genetics Center | RCV000006925 | SCV002580717 | likely pathogenic | Ectrodactyly, ectodermal dysplasia, and cleft lip-palate syndrome 3 | 2022-04-04 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000006925 | SCV000027121 | pathogenic | Ectrodactyly, ectodermal dysplasia, and cleft lip-palate syndrome 3 | 2011-01-01 | no assertion criteria provided | literature only | |
OMIM | RCV000006926 | SCV000027122 | pathogenic | ADULT syndrome | 2011-01-01 | no assertion criteria provided | literature only | |
Bioscientia Institut fuer Medizinische Diagnostik Gmb |
RCV000006925 | SCV000537817 | pathogenic | Ectrodactyly, ectodermal dysplasia, and cleft lip-palate syndrome 3 | no assertion criteria provided | clinical testing | ||
Gharavi Laboratory, |
RCV000413620 | SCV000809433 | pathogenic | not provided | 2018-09-16 | no assertion criteria provided | research |