Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| New York Genome Center | RCV000754089 | SCV001441335 | pathogenic | Intellectual disability, autosomal dominant 22 | 2020-02-23 | criteria provided, single submitter | clinical testing | The c.1391G>A (p.Arg464His) variant identified in the ZBTB18 gene substitutes a completely conserved Arginine for Histidine at amino acid 455/523 (coding exon 2/2). This variant is absent from gnomAD suggesting it is not a common benign variant in the populations represented in this database. In silico algorithms predict this variant to be Deleterious (Provean; score: -3.44) and Damaging (SIFT; score: 0.001) to the function of the canonical transcript. The p.Arg464 (UniProtKB; Q99592) is in the Zinc Finger domain of the protein. This variant is reported as Pathogenic in ClinVar (VarID:617452), and a different amino acid change at the same amino acid is also reported as Pathogenic in ClinVar (p.Arg464Cys; VarID:440857). The p.Arg464His variant identified in this individual has been reported previously in three affected individuals in the literature [PMID:28135719; PMID:28283832; PMID:29573576]. This variant was detected de novo in an individual submitted for clinical WGS. The c.1391G>A (p.Arg464His) variant identified here is reported here as Pathogenic. |
| Clinical Genetics and Genomics, |
RCV001269922 | SCV001450283 | likely pathogenic | not provided | 2016-06-30 | criteria provided, single submitter | clinical testing | |
| Molecular Genetics Lab, |
RCV000754089 | SCV004697738 | pathogenic | Intellectual disability, autosomal dominant 22 | criteria provided, single submitter | clinical testing | ||
| Labcorp Genetics |
RCV001269922 | SCV005834298 | pathogenic | not provided | 2024-11-12 | 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 464 of the ZBTB18 protein (p.Arg464His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with ZBTB18-related conditions (PMID: 29573576). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 617452). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt ZBTB18 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. |
| OMIM | RCV000754089 | SCV000882424 | pathogenic | Intellectual disability, autosomal dominant 22 | 2022-04-05 | no assertion criteria provided | literature only |