ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.357C>G (p.Phe119Leu) (rs1559428077)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000767262 SCV000897811 pathogenic Von Hippel-Lindau syndrome 2018-08-01 criteria provided, single submitter clinical testing
Invitae RCV000821822 SCV000962594 pathogenic Erythrocytosis, familial, 2; Von Hippel-Lindau syndrome 2018-08-14 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with leucine at codon 119 of the VHL protein (p.Phe119Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with von Hippel-Lindau syndrome (PMID: 7728151, 12000816) and in an individual affected with pheochromocytomas (PMID: 19336503). Experimental studies have shown that this missense change impairs protein stability and function (PMID: 23840444, 21715564). A different variant (c.355T>C) giving rise to the same protein effect observed here (p.Phe119Leu) has been reported in an individual affected with von Hippel-Lindau syndrome (PMID: 16142346, 19270817), indicating that this residue may be critical for protein function. For these reasons, this variant has been classified as Pathogenic.

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