ClinVar Miner

Submissions for variant NM_152564.5(VPS13B):c.6947A>G (p.Tyr2316Cys)

gnomAD frequency: 0.00001  dbSNP: rs386834104
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000050098 SCV001202767 uncertain significance Cohen syndrome 2022-10-03 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 2341 of the VPS13B protein (p.Tyr2341Cys). This variant is present in population databases (rs386834104, gnomAD 0.01%). This missense change has been observed in individual(s) with Cohen syndrome (PMID: 15154116). ClinVar contains an entry for this variant (Variation ID: 56685). 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. 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.
Fulgent Genetics, Fulgent Genetics RCV000050098 SCV002793834 uncertain significance Cohen syndrome 2022-04-14 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003905014 SCV004722705 uncertain significance VPS13B-related disorder 2023-11-08 criteria provided, single submitter clinical testing The VPS13B c.6947A>G variant is predicted to result in the amino acid substitution p.Tyr2316Cys. The VPS13B gene was previously known as COH1 with this variant being described using alternative nomenclature of c.7022A>G (p.Tyr2341Cys). This variant was reported in the compound heterozygous state along with a truncating variant in a patient with Cohen syndrome (Hennies et al. 2004. PubMed ID: 15154116). This variant is reported in 0.0096% of alleles in individuals of Ashkenazi Jewish descent in gnomAD (http://gnomad.broadinstitute.org/variant/8-100733172-A-G). Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000050098 SCV000082507 probable-pathogenic Cohen syndrome no assertion criteria provided not provided Converted during submission to Likely pathogenic.
Natera, Inc. RCV000050098 SCV002082630 uncertain significance Cohen syndrome 2020-10-15 no assertion criteria provided clinical testing

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