ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.490C>T (p.Gln164Ter) (rs5030819)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000485182 SCV000567988 pathogenic not provided 2015-09-15 criteria provided, single submitter clinical testing The Q164X variant has been published previously in association with von Hippel-Lindau (VHL) syndrome and pheochromocytoma (Hes et al., 2007; Galvac et al., 1996; Neumann et al., 2002). It is predicted to cause loss of normal protein function through protein truncation as the last 50 amino acid residues are lost. In addition, Q146X was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Given the available evidence, we interpret Q164X as a pathogenic variant.
Center for Human Genetics, Inc,Center for Human Genetics, Inc RCV000208820 SCV000782419 pathogenic Von Hippel-Lindau syndrome 2016-11-01 criteria provided, single submitter clinical testing
Invitae RCV000792769 SCV000932089 pathogenic Erythrocytosis, familial, 2; Von Hippel-Lindau syndrome 2018-10-04 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the VHL gene (p.Gln164*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 50 amino acids of the VHL protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with von Hippel-Lindau syndrome (PMID: 8707293, 26920352, 9829911, 8956040). ClinVar contains an entry for this variant (Variation ID: 223228). This variant disrupts the C-terminus of the VHL protein. Other variant(s) that disrupt this region (p.Ser183*) have been determined to be pathogenic (PMID: 8707293, 10567493, 11309459). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000208820 SCV000264762 likely pathogenic Von Hippel-Lindau syndrome 2016-02-26 no assertion criteria provided clinical testing

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