ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.496G>T (p.Val166Phe) (rs104893825)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000220823 SCV000274633 pathogenic Hereditary cancer-predisposing syndrome 2016-06-14 criteria provided, single submitter clinical testing The p.V166F pathogenic mutation (also known as c.496G>T), located in coding exon 3 of the VHL gene, results from a G to T substitution at nucleotide position 496. The valine at codon 166 is replaced by phenylalanine, an amino acid with highly similar properties. This alteration has been reported in multiple individuals with a clinical diagnosis of Von Hippel-Lindau syndrome; including personal histories of pheochromocytoma (Cruz JB et al, Arq Bras Endocrinol Metabol 2007 Dec; 51(9):1463-7; Gross DJet al.J. Clin. Endocrinol. Metab. 1996 Jan; 81(1):147-9; Nordstrom-O'Brien Met al.Hum. Mutat.2010May;31(5):521-37;Maher ERet al.J. Med. Genet. 1996 Apr; 33(4):328-32); head and neck paraganglioma, pheochromocytoma and CNS hemangiblastoma (Boedeker CCet al.J. Clin. Endocrinol. Metab. 2009 Jun; 94(6):1938-44); as well as retinal hemangioblastoma (Dollfus Het al.Invest. Ophthalmol. Vis. Sci. 2002 Sep; 43(9):3067-74). In addition, in vitro experiments suggest that mutations affecting residue 166, such as p.V166F, lead to a partial loss of elongin-binding activity(Ohh Met al.J.Clin. Invest. 1999 Dec; 104(11):1583-91). Of note, this alteration is also referred to as 709G>T in published literature.This alteration has been determined to be de novo in an affected individual in our cohort (Ambry internal data). Based on the available evidence, p.V166F is classified as a pathogenic mutation.
OMIM RCV000002310 SCV000022468 pathogenic Von Hippel-Lindau syndrome 1996-01-01 no assertion criteria provided literature only

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