ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.355T>C (p.Phe119Leu) (rs1553619948)

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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 RCV000588483 SCV000697505 pathogenic Von Hippel-Lindau syndrome 2016-02-05 criteria provided, single submitter clinical testing Variant summary: The c.355T>C (F119L) in VHL is a missense variant involving a highly conserved nucleotide and 3/4 in silico tools predict this variant to be deleterious (no prediction for SIFT). The variant was not found in the general population but was reported in at least 3 VHL patients. Another variant, c.357C>G, leading to the same amino acid change (F119L) and c.356T>C (F119S) have been reported in multiple VHL pts, indicating that this codon is a mutation hotspot. Additionally this variant has been identified as a somatic mutation in multiple renal cell carcinomas. Taken together, this is a disease variant and was classified as Pathogenic.
Invitae RCV000631289 SCV000752317 pathogenic Erythrocytosis, familial, 2; Von Hippel-Lindau syndrome 2017-10-27 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 reported in individuals affected with von Hippel-Lindau  (VHL) disease  (PMID: 16142346, 19270817). This variant is also known as P190L in the literature. Furthermore, a different nucleotide change at this position (c.357C>G) which results in the same amino acid change has been reported in individuals with VHL (PMID:  7728151, 12000816). Experimental studies have shown that this missense change causes a deleterious effect on protein stability and function (PMID: 23840444, 21715564). For these reasons, this variant has been classified as Pathogenic.

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