ClinVar Miner

Submissions for variant NM_015178.3(RHOBTB2):c.1834G>A (p.Val612Ile)

gnomAD frequency: 0.00001  dbSNP: rs1158005108
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001934416 SCV002208987 uncertain significance not provided 2021-02-01 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 634 of the RHOBTB2 protein (p.Val634Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with RHOBTB2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 RCV003339844 SCV004047593 uncertain significance Developmental and epileptic encephalopathy, 64 criteria provided, single submitter clinical testing The missense variant in c.1834G>A in RHOBTB2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Val612Ile variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. This variant has been reported to the ClinVar database as Variant of Uncertain Significance (VUS). The amino acid change p.Val612Ile in RHOBTB2 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Val at position 612 is changed to a Ile changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as Uncertain Significance (VUS).
PreventionGenetics, part of Exact Sciences RCV003401932 SCV004104592 uncertain significance RHOBTB2-related disorder 2022-09-22 criteria provided, single submitter clinical testing The RHOBTB2 c.1900G>A variant is predicted to result in the amino acid substitution p.Val634Ile. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Ambry Genetics RCV004656764 SCV005162126 uncertain significance Inborn genetic diseases 2024-05-20 criteria provided, single submitter clinical testing The c.1900G>A (p.V634I) alteration is located in exon 10 (coding exon 8) of the RHOBTB2 gene. This alteration results from a G to A substitution at nucleotide position 1900, causing the valine (V) at amino acid position 634 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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