ClinVar Miner

Submissions for variant NM_152564.5(VPS13B):c.1876C>A (p.Pro626Thr)

dbSNP: rs1027919525
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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 RCV000818784 SCV000959416 uncertain significance Cohen syndrome 2024-01-26 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 626 of the VPS13B protein (p.Pro626Thr). This variant is not present in population databases (gnomAD no frequency). 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: 661380). 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 not expected to disrupt VPS13B protein function with a negative 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.
GeneDx RCV002221586 SCV002499000 uncertain significance not provided 2023-04-24 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV004686618 SCV005174713 uncertain significance Inborn genetic diseases 2024-05-29 criteria provided, single submitter clinical testing The c.1876C>A (p.P626T) alteration is located in exon 14 (coding exon 13) of the VPS13B gene. This alteration results from a C to A substitution at nucleotide position 1876, causing the proline (P) at amino acid position 626 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV000818784 SCV002079490 uncertain significance Cohen syndrome 2020-10-13 no assertion criteria provided clinical testing

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