ClinVar Miner

Submissions for variant NM_017890.4(VPS13B):c.3811A>T (p.Thr1271Ser) (rs142674934)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000719533 SCV000850401 uncertain significance History of neurodevelopmental disorder 2017-01-27 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724113 SCV000228257 uncertain significance not provided 2017-01-11 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000515402 SCV000611529 uncertain significance Cohen syndrome 2017-05-23 criteria provided, single submitter clinical testing
GeneDx RCV000724113 SCV000564895 uncertain significance not provided 2016-07-11 criteria provided, single submitter clinical testing The T1271S variant in the VPS13B gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This 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 T1271S variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret T1271S as a variant of uncertain significance.
Genetic Services Laboratory, University of Chicago RCV000193659 SCV000249409 uncertain significance not specified 2014-04-14 criteria provided, single submitter clinical testing
Invitae RCV000515402 SCV000630872 uncertain significance Cohen syndrome 2018-04-24 criteria provided, single submitter clinical testing This sequence change replaces threonine with serine at codon 1271 of the VPS13B protein (p.Thr1271Ser). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and serine. This variant is present in population databases (rs142674934, ExAC 0.1%). This variant has not been reported in the literature in individuals with a VPS13B-related disease. ClinVar contains an entry for this variant (Variation ID: 195900). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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