ClinVar Miner

Submissions for variant NM_015178.3(RHOBTB2):c.208C>T (p.Arg70Ter)

dbSNP: rs1215059455
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Breda Genetics srl RCV001328473 SCV001519520 uncertain significance Developmental and epileptic encephalopathy, 64 2020-10-23 criteria provided, single submitter clinical testing The variant c.274C>T (p.Arg92*) in the RHOBTB2 is predicted to create a premature stop codon at amino acid position Arg92, which is likely to result in a truncated protein or protein loss due to nonsense-mediated messenger decay (NMD). There is no information on frequency in gnomAD, 1000 Genomes or NHLI Exome Sequencing Project (ESP). It is important to highlight that only missense variants have been reported as pathogenic so far, as RHOBTB2 mutations seem to result more likely in altered protein function rather than haploinsufficiency or a loss of function (Straub et al., 2018, PMID: 29276004). Therefore, despite its predicted impact as nonsense mutation, we interpret this variant as of uncertain significance, without excluding the possibility that it’s actually a rare benign variant.
CeGaT Center for Human Genetics Tuebingen RCV003438742 SCV004164488 uncertain significance not provided 2022-03-01 criteria provided, single submitter clinical testing RHOBTB2: PM2
Labcorp Genetics (formerly Invitae), Labcorp RCV003438742 SCV004484601 uncertain significance not provided 2023-02-08 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg92*) in the RHOBTB2 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in RHOBTB2 cause disease. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RHOBTB2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1027644). 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 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.