ClinVar Miner

Submissions for variant NM_015243.2(VPS13B):c.1700G>A (p.Gly567Glu) (rs141046414)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000487581 SCV000113816 uncertain significance not provided 2017-12-19 criteria provided, single submitter clinical testing
Ambry Genetics RCV000210673 SCV000262849 uncertain significance Inborn genetic diseases 2017-06-12 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Illumina Clinical Services Laboratory,Illumina RCV000350196 SCV000470770 uncertain significance Cohen syndrome 2016-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000487581 SCV000564893 uncertain significance not provided 2016-11-08 criteria provided, single submitter clinical testing The G567E variant in the VPS13B gene has not been reported previously in a patient with Cohen syndrome who was also heterozygous for a second VPS13B variant, however, clinical history and familial segregation information were not included (Farwell et al., 2015). The G567E variant was not observed at any significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The G567E variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved across species, and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret G567E as a variant of uncertain significance.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000487581 SCV000575566 uncertain significance not provided 2016-09-01 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000081881 SCV000597877 uncertain significance not specified 2017-03-14 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000350196 SCV000611526 uncertain significance Cohen syndrome 2017-05-23 criteria provided, single submitter clinical testing
Invitae RCV000350196 SCV000826266 uncertain significance Cohen syndrome 2018-06-11 criteria provided, single submitter clinical testing This sequence change replaces glycine with glutamic acid at codon 567 of the VPS13B protein (p.Gly567Glu). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant is present in population databases (rs141046414, ExAC 0.06%). This variant has been reported in an individual affected with Cohen syndrome (PMID: 25356970). ClinVar contains an entry for this variant (Variation ID: 95834). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
GenomeConnect, ClinGen RCV000350196 SCV000784700 not provided Cohen syndrome no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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