ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.351G>T (p.Trp117Cys) (rs727504215)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000723964 SCV000203788 pathogenic not provided 2014-04-24 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000154124 SCV000697504 pathogenic Von Hippel-Lindau syndrome 2016-02-03 criteria provided, single submitter clinical testing Variant summary: The variant of interest causes a missense change involving a conserved nucleotide with 5/5 in silico programs predicting a "deleterious" outcome. The variant of interest was not observed in controls (ExAC, 1000 Gs or ESP) but has been reported in multiple affected individuals via publications, along with reputable databases/clinical laboratories citing the variant with a classification of "pathogenic." Therefore, taking all available lines of evidence, the variant of interest is classified as Pathogenic.
Ambry Genetics RCV001020510 SCV001181999 pathogenic Hereditary cancer-predisposing syndrome 2018-06-27 criteria provided, single submitter clinical testing The p.W117C pathogenic mutation (also known as c.351G>T), located in coding exon 2 of the VHL gene, results from a G to T substitution at nucleotide position 351. The tryptophan at codon 117 is replaced by cysteine, an amino acid with highly dissimilar properties. In one family of Arabic and Persian descent, this mutation was shown to segregate with disease in thirteen family members affected with Von Hippel<span style="color:rgb(84, 84, 84); font-family:roboto,arial,sans-serif; font-size:small">-Lindau<span style="color:rgb(84, 84, 84); font-family:roboto,arial,sans-serif; font-size:small"> (VHL) syndrome and was not seen in healthy members of the family or in 55 healthy control subjects (AlFadhli SM, Med Princ Pract 2008 ; 17(5):395-9). Additionally, this mutation has been identified in various other families fulfilling diagnostic criteria for VHL (Chen F, Hum. Mutat. 1995 ; 5(1):66-75. Olschwang S, Hum. Mutat. 1998 ; 12(6):424-30; Dollfus H et al. Invest. Ophthalmol. Vis. Sci., 2002 Sep;43:3067-74;Gallou C et al. Hum. Mutat., 2004 Sep;24:215-24). Of note, this alteration is also designated as G564T (Tryp117Cys) in published literature. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, p.W117C is classified as a pathogenic mutation.
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000154124 SCV000264722 pathogenic Von Hippel-Lindau syndrome 2016-02-26 no assertion criteria provided clinical testing

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