ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.69C>A (p.Tyr23Ter)

dbSNP: rs1553619313
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000663119 SCV000786248 uncertain significance Von Hippel-Lindau syndrome 2018-03-26 criteria provided, single submitter clinical testing
Ambry Genetics RCV002360687 SCV002665204 uncertain significance Hereditary cancer-predisposing syndrome 2022-09-13 criteria provided, single submitter clinical testing The p.Y23* variant (also known as c.69C>A), located in coding exon 1 of the VHL gene, results from a C to A substitution at nucleotide position 69. This changes the amino acid from a tyrosine to a stop codon within coding exon 1.Premature stop codons are typically deleterious in nature; however, an alternate initiation codon exists 31 amino acids downstream from this alteration, and is reported to result in a biologically active isoform known as VHL 19 (Iliopoulos O et al, Proc. Natl. Acad. Sci. U.S.A. 1998 Sep; 95(20):11661-6. Schoenfeld A et al, Proc. Natl. Acad. Sci. U.S.A. 1998 Jul; 95(15):8817-22). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV002530602 SCV002945260 uncertain significance Chuvash polycythemia; Von Hippel-Lindau syndrome 2023-11-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr23*) in the VHL gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 191 amino acid(s) of the VHL protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with VHL-related conditions. ClinVar contains an entry for this variant (Variation ID: 548874). 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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