ClinVar Miner

Submissions for variant NM_152564.5(VPS13B):c.11143C>T (p.Arg3715Trp)

gnomAD frequency: 0.00001  dbSNP: rs772640414
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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 RCV000634113 SCV000755393 uncertain significance Cohen syndrome 2024-01-08 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 3740 of the VPS13B protein (p.Arg3740Trp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 528853). 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) performed at Invitae 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.
Ambry Genetics RCV002438673 SCV002748573 uncertain significance Inborn genetic diseases 2018-04-06 criteria provided, single submitter clinical testing The p.R3740W variant (also known as c.11218C>T), located in coding exon 57 of the VPS13B gene, results from a C to T substitution at nucleotide position 11218. The arginine at codon 3740 is replaced by tryptophan, an amino acid with dissimilar 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.
PreventionGenetics, part of Exact Sciences RCV003424205 SCV004116746 uncertain significance VPS13B-related disorder 2023-09-26 criteria provided, single submitter clinical testing The VPS13B c.11143C>T variant is predicted to result in the amino acid substitution p.Arg3715Trp. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0021% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/8-100874102-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Natera, Inc. RCV000634113 SCV001454479 uncertain significance Cohen syndrome 2020-04-15 no assertion criteria provided clinical testing

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