Submissions for variant NM_015178.3(RHOBTB2):c.2034C>G (p.Tyr678Ter)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Institute of Human Genetics, University of Leipzig Medical Center	RCV004759342	SCV005368044	uncertain significance	Developmental and epileptic encephalopathy, 64	2024-05-29	criteria provided, single submitter	clinical testing	Criteria applied: PVS1_MOD,PM2,PM3_SUP
PreventionGenetics, part of Exact Sciences	RCV003962073	SCV004781697	uncertain significance	RHOBTB2-related disorder	2024-01-03	no assertion criteria provided	clinical testing	The RHOBTB2 c.2100C>G variant is predicted to result in premature protein termination (p.Tyr700*). To our knowledge, this variant has not been reported in the literature. The normal protein terminates at codon 750. To our knowledge, no truncating variants result in a premature protein termination downstream of this variant. And only a limited number of truncating variants have been reported in the literature and the role of this type of variants in this gene is largely unknown (Human Gene Mutation Database). This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/8-22874832-C-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.