ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.407T>G (p.Phe136Cys) (rs5030833)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000589290 SCV000697514 pathogenic Hereditary cancer-predisposing syndrome 2016-02-10 criteria provided, single submitter clinical testing Variant summary: VHL c.407T>G variant affects a conserved nucleotide, resulting in amino acid change from an aromatic Phe to a medium sized polar Cys. 4/4 in-silico tools predict damaging outcome for this variant (Mutation Taster not captured due to low p-value). Hif1-alpha regulation has been strongly correlated with hemangioblastoma susceptibility; and functional studies have shown that F136C disrupts binding to Hif1-alpha and elongin C, and reduces binding affinity for TBP-1 (Corn_NG_2003). This variant is not found in 121412 control chromosomes; however, it has been cited in at least 5 patients with pheochromocytoma and 1 patient with haemangioblastoma of the CNS. Taken together, this is a disease variant and was classified as pathogenic.
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000767268 SCV000897819 uncertain significance Von Hippel-Lindau syndrome 2018-08-01 criteria provided, single submitter clinical testing

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