ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.551T>C (p.Leu184Pro) (rs1064793878)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000484822 SCV000567249 pathogenic not provided 2015-07-28 criteria provided, single submitter clinical testing The L184P variant has been published previously in association von Hippel-Lindau disease without pheochromocytoma(Zbar et al., 1996). It was not observed in approximately 6,500 individuals of European and African Americanancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in thesepopulations. L184P is a semi-conservative amino acid substitution, which may impact secondary proteinstructure as these residues differ in some properties. This substitution occurs at a position that is conservedacross species and in-silico analysis predicts this variant is probably damaging to the proteinstructure/function. In addition, missense variants at the same codon (L184R/H) and in nearby residues(S183L, D179N, I180V, E186K, L188V/P/R/E) have also been reported in the Human Gene MutationDatabase in association with VHL-related disorders (Stenson et al., 2014), supporting the functionalimportance of this region of the protein. Therefore, we consider the L184P variant to be pathogenic.

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