ClinVar Miner

Submissions for variant NM_152564.5(VPS13B):c.827G>A (p.Arg276His)

gnomAD frequency: 0.00001  dbSNP: rs181021782
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001067552 SCV001232619 uncertain significance Cohen syndrome 2024-10-17 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 276 of the VPS13B protein (p.Arg276His). This variant is present in population databases (rs181021782, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with VPS13B-related conditions. ClinVar contains an entry for this variant (Variation ID: 861110). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt VPS13B protein function with a positive predictive value of 80%. 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.
Mayo Clinic Laboratories, Mayo Clinic RCV001507741 SCV001713476 uncertain significance not provided 2019-12-18 criteria provided, single submitter clinical testing
Ambry Genetics RCV002429725 SCV002680170 uncertain significance Inborn genetic diseases 2018-03-18 criteria provided, single submitter clinical testing The p.R276H variant (also known as c.827G>A), located in coding exon 6 of the VPS13B gene, results from a G to A substitution at nucleotide position 827. The arginine at codon 276 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001067552 SCV001454220 uncertain significance Cohen syndrome 2020-03-10 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV003396715 SCV004119864 uncertain significance VPS13B-related disorder 2024-05-07 no assertion criteria provided clinical testing The VPS13B c.827G>A variant is predicted to result in the amino acid substitution p.Arg276His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0046% of alleles in individuals of European (Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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