ClinVar Miner

Submissions for variant NM_015178.3(RHOBTB2):c.1453C>T (p.Arg485Cys)

dbSNP: rs1563292586
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
SIB Swiss Institute of Bioinformatics RCV000755717 SCV000883194 likely pathogenic Developmental and epileptic encephalopathy, 64 2018-10-15 criteria provided, single submitter curation This variant is interpreted as Likely Pathogenic, for Epileptic encephalopathy, early infantile, 64, autosomal dominant. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PS2 => De novo (paternity and maternity confirmed) (
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München RCV000755717 SCV001150238 pathogenic Developmental and epileptic encephalopathy, 64 2019-08-07 criteria provided, single submitter clinical testing
Invitae RCV001052516 SCV001216728 pathogenic not provided 2024-01-18 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 507 of the RHOBTB2 protein (p.Arg507Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with RHOBTB2-related conditions (PMID: 33504645, 33619735; Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 617912). 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) performed at Invitae indicates that this missense variant is not expected to disrupt RHOBTB2 protein function with a negative predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen RCV001052516 SCV001501451 likely pathogenic not provided 2023-09-01 criteria provided, single submitter clinical testing RHOBTB2: PS2, PM2, PS4:Moderate
Institute of Human Genetics, University of Leipzig Medical Center RCV000755717 SCV002549849 likely pathogenic Developmental and epileptic encephalopathy, 64 2022-07-04 criteria provided, single submitter clinical testing This variant was identified as de novo (maternity and paternity confirmed)._x000D_ Criteria applied: PS2, PS4_MOD, PM1, PM2_SUP, PP3
Illumina Laboratory Services, Illumina RCV000755717 SCV004014710 pathogenic Developmental and epileptic encephalopathy, 64 2023-02-10 criteria provided, single submitter clinical testing The RHOBTB2 c.1519C>T (p.Arg507Cys) missense variant results in the substitution of arginine at amino acid position 507 with cysteine. This variant has been reported in a heterozygous state in a total of three individuals with developmental and epileptic encephalopathy, including two individuals in whom the variant was found in a de novo state and one individual in whom the inhertiance of the variant was unknown (PMID: 29768694; PMID: 33619735; PMID: 33504645). This variant is not found in version 2.1.1 or version 3.1.2 of the Genome Aggregation Database. Transient expression in Neuro2a cells demonstrated that the p.Arg507Cys variant was significantly more abundant than wild-type and escaped protesomal degradation. Co-expression of CUL3 with RHOBTB2 resulted in a decrease in levels of wild-type RHOBTB2 but not that of the variant protein suggesting that the variant affects degradation by the CUL3 ubiquitin ligase complex (PMID: 29768694). The Arg507 residue is located at the C-terminal end of the first BTB domain with several clinically significant missense variants reported in the vicinity (PMID: 29276004). Based on the available evidence, the c.1519C>T (p.Arg507Cys) variant is classified as pathogenic for developmental and epileptic encephalopathy.
GeneDx RCV001052516 SCV004036902 pathogenic not provided 2023-09-22 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 29768694, 37090824, 37165955, 33619735)
Institute of Human Genetics, Heidelberg University RCV000755717 SCV004803178 likely pathogenic Developmental and epileptic encephalopathy, 64 2020-05-15 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.