ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.483_500dup (p.Cys162_Arg167dup) (rs1553620312)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000564563 SCV000664697 likely pathogenic Hereditary cancer-predisposing syndrome 2017-11-02 criteria provided, single submitter clinical testing The c.483_500dup18 pathogenic mutation (also known as p.C162_R167dup), located in coding exon 3 of the VHL gene, results from an in-frame duplication of 18 nucleotides at nucleotide positions 483 to 500. This results in the duplication of 6 extra residues (CLQVVR) between codons 162 and 167. Based on internal structural assessment, this alteration inhibits elongin binding (Van Molle I et al. Chem. Biol. 2012 Oct;19(10):1300-12). Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000767278 SCV000897832 uncertain significance Von Hippel-Lindau syndrome 2018-08-01 criteria provided, single submitter clinical testing
Invitae RCV001373035 SCV001569733 uncertain significance Erythrocytosis, familial, 2; Von Hippel-Lindau syndrome 2020-10-04 criteria provided, single submitter clinical testing This variant, c.483_500dup, results in the insertion of 6 amino acid(s) to the VHL protein (p.Cys162_Arg167dup), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of von Hippel-Lindau syndrome (Invitae). ClinVar contains an entry for this variant (Variation ID: 480846). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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