ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.593T>C (p.Leu198Pro) (rs869025667)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000208871 SCV000597846 likely pathogenic Von Hippel-Lindau syndrome 2016-12-30 criteria provided, single submitter clinical testing
Ambry Genetics RCV001024703 SCV001186771 likely pathogenic Hereditary cancer-predisposing syndrome 2018-10-04 criteria provided, single submitter clinical testing The p.L198P variant (also known as c.593T>C), located in coding exon 3 of the VHL gene, results from a T to C substitution at nucleotide position 593. The leucine at codon 198 is replaced by proline, an amino acid with similar properties. This variant has been reported as de novo in a Swedish patient meeting clinical diagnostic criteria for von Hippel-Lindau syndrome (VHL): he was diagnosed with a pancreatic neuroendocrine tumor at age 15y and a retinal hemangioblastoma and bilateral pheochromocytomas at age 16y (Wittstrom E et al. Ophthalmic Genet. 2014 Jun;35(2):91-106). This variant has also been detected in a patient with a personal and family history of bilateral pheochromocytomas (Lomte N et al. Fam Cancer. 2018 Jul;17(3):441-449). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Based on internal structural analysis, this variant is anticipated to result in a significant decrease in structural stability (Ambry internal data). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
University Health Network Clinical Genomics Labs,University Health Network RCV000208871 SCV001950143 uncertain significance Von Hippel-Lindau syndrome 2019-08-20 criteria provided, single submitter clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000208871 SCV000264775 likely pathogenic Von Hippel-Lindau syndrome 2016-02-26 no assertion criteria provided clinical testing

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