ClinVar Miner

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

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Total submissions: 2
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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.
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine RCV001258069 SCV001434901 likely pathogenic Von Hippel-Lindau syndrome 2020-02-12 criteria provided, single submitter clinical testing This c. 551T>C variant in the VHL gene replaces leucine with proline at codon 184 of the VHL protein (p.Leu184Pro). This variant has been reported in individuals with Von Hippel-Lindau disease and sporadic conventional renal cell carcinoma (PMID: 8956040, 9681856, 9829911, 10408776, 14722919, 19996202, 22825683, 26763786). This variant is absent from general population databases (gnomAD). Another variant that disrupts the same residue (p.Leu184Arg) has been reported in individual affected with Von Hippel-Lindau disease (PMID: 9681856). Multiple lines of in silico algorithms have predicted this p.Leu184Pro variant may be deleterious. Therefore, this c.551T>C variant is classified as likely pathogenic

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