ClinVar Miner

Submissions for variant NM_152564.5(VPS13B):c.1391A>C (p.Lys464Thr)

gnomAD frequency: 0.00001  dbSNP: rs1431957435
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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 RCV001050967 SCV001215100 uncertain significance Cohen syndrome 2022-10-27 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 464 of the VPS13B protein (p.Lys464Thr). This variant is present in population databases (no rsID available, 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: 847426). 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. 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 RCV002393251 SCV002700035 uncertain significance Inborn genetic diseases 2019-03-26 criteria provided, single submitter clinical testing The p.K464T variant (also known as c.1391A>C), located in coding exon 9 of the VPS13B gene, results from an A to C substitution at nucleotide position 1391. The lysine at codon 464 is replaced by threonine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001050967 SCV002079469 uncertain significance Cohen syndrome 2021-03-20 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004743266 SCV005348217 uncertain significance VPS13B-related disorder 2024-06-19 no assertion criteria provided clinical testing The VPS13B c.1391A>C variant is predicted to result in the amino acid substitution p.Lys464Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0087% of alleles in individuals of Latino 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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