ClinVar Miner

Submissions for variant NM_152564.5(VPS13B):c.10633A>T (p.Met3545Leu)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003060177 SCV003448190 uncertain significance Cohen syndrome 2022-09-19 criteria provided, single submitter clinical testing This sequence change replaces methionine with leucine at codon 3570 of the VPS13B protein (p.Met3570Leu). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and leucine. This variant is present in population databases (rs781672013, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with VPS13B-related conditions. 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 RCV003060176 SCV003589538 uncertain significance Inborn genetic diseases 2021-11-09 criteria provided, single submitter clinical testing The c.10708A>T (p.M3570L) alteration is located in exon 56 (coding exon 55) of the VPS13B gene. This alteration results from a A to T substitution at nucleotide position 10708, causing the methionine (M) at amino acid position 3570 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV003410055 SCV004113361 uncertain significance VPS13B-related disorder 2022-09-23 criteria provided, single submitter clinical testing The VPS13B c.10633A>T variant is predicted to result in the amino acid substitution p.Met3545Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.045% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/8-100866250-A-T). 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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