ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.363dup (p.Ala122fs) (rs1575927767)

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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 RCV001020780 SCV001182304 pathogenic Hereditary cancer-predisposing syndrome 2018-08-28 criteria provided, single submitter clinical testing The c.363dupT pathogenic mutation, located in coding exon 2 of the VHL gene, results from a duplication of T at nucleotide position 363, causing a translational frameshift with a predicted alternate stop codon (p.A122Cfs*10). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Invitae RCV001216349 SCV001388143 pathogenic Erythrocytosis, familial, 2; Von Hippel-Lindau syndrome 2019-06-15 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the VHL gene (p.Ala122Cysfs*10). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 92 amino acids of the VHL protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with VHL-related conditions. 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.

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