ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.497T>C (p.Val166Ala) (rs397516445)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000036549 SCV000060204 pathogenic Von Hippel-Lindau syndrome 2012-09-11 criteria provided, single submitter clinical testing The Val166Ala variant has previously been reported to have occurred de novo in a n individual with clinical features of Von Hippel-Lindau syndrome and has been i dentified in one affected individual previously tested by our laboratory (Hes 20 07, LMM unpublished data). Valine (Val) at position 166 is not evolutionarily co nserved in mammals (rabbit and pika have an isoleucine at this position), howeve r, a different amino acid change at this location (Val166Phe) has also been asso ciated with the clinical features of Von Hippel-Lindau syndrome (Maher 1996). Co mputational analyses (biochemical amino acid properties, conservation, AlignGVGD , PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein, but structural evidence suggests this amino acid plays an importan t role in VHL function (Stebbins 1999). In summary, this variant is highly likel y to be pathogenic based on its de novo occurrence in a patient with sporadic di sease.
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000036549 SCV000897837 pathogenic Von Hippel-Lindau syndrome 2018-08-01 criteria provided, single submitter clinical testing

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