ClinVar Miner

Submissions for variant NM_015178.3(RHOBTB2):c.2038C>T (p.Arg680Trp)

gnomAD frequency: 0.00001  dbSNP: rs767630251
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
New York Genome Center RCV001420641 SCV001622966 uncertain significance Developmental and epileptic encephalopathy, 64 2020-06-12 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001882534 SCV002118393 uncertain significance not provided 2023-12-28 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 702 of the RHOBTB2 protein (p.Arg702Trp). This variant is present in population databases (rs767630251, gnomAD 0.006%). 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: 1098681). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on RHOBTB2 protein function. 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.
Neuberg Centre For Genomic Medicine, NCGM RCV001420641 SCV004176510 uncertain significance Developmental and epileptic encephalopathy, 64 2023-02-14 criteria provided, single submitter clinical testing The missense c.2038C>T(p.Arg680Trp) variant in RHOBTB2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The variant is reported with an allele frequency of 0.001% in the gnomAD exomes database and is novel (not in any individuals) in 1000 Genomes database. This variant has been reported to the ClinVar database as Uncertain significance. The amino acid change p.Arg680Trp in RHOBTB2 is predicted as conserved by PhyloP across 100 vertebrates. The amino acid Arg at position 680 is changed to a Trp changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as Variant of Uncertain Significance (VUS).
Ambry Genetics RCV004656590 SCV005162118 uncertain significance Inborn genetic diseases 2024-05-20 criteria provided, single submitter clinical testing The c.2104C>T (p.R702W) alteration is located in exon 12 (coding exon 10) of the RHOBTB2 gene. This alteration results from a C to T substitution at nucleotide position 2104, causing the arginine (R) at amino acid position 702 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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.