ClinVar Miner

Submissions for variant NM_152564.5(VPS13B):c.7151C>T (p.Pro2384Leu)

gnomAD frequency: 0.00005  dbSNP: rs183874686
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000193148 SCV000249417 uncertain significance not specified 2015-03-12 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000815411 SCV000955862 uncertain significance Cohen syndrome 2024-01-16 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 2409 of the VPS13B protein (p.Pro2409Leu). This variant is present in population databases (rs183874686, gnomAD 0.01%). 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: 212580). 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 RCV002372166 SCV002671397 uncertain significance Inborn genetic diseases 2018-02-14 criteria provided, single submitter clinical testing The p.P2409L variant (also known as c.7226C>T), located in coding exon 39 of the VPS13B gene, results from a C to T substitution at nucleotide position 7226. The proline at codon 2409 is replaced by leucine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV000815411 SCV002082634 uncertain significance Cohen syndrome 2019-11-11 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004742326 SCV005365598 uncertain significance VPS13B-related disorder 2024-03-05 no assertion criteria provided clinical testing The VPS13B c.7151C>T variant is predicted to result in the amino acid substitution p.Pro2384Leu. To our knowledge, this variant has not been reported in the literature in any individuals diagnosed with Cohen syndrome. This variant is reported in 0.013% of alleles in individuals of European (Non-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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