ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.463+4C>T (rs879253989)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000679042 SCV000293080 uncertain significance not provided 2016-07-14 criteria provided, single submitter clinical testing This variant is denoted VHL c.463+4C>T or IVS2+4C>T and consists of a C>T nucleotide substitution at the +4 position of intron 2 of the VHL gene. Multiple in silico models predict that this variant has no effect on gene splicing; however, in the absence of RNA or functional studies, the actual effect of this variant is unknown. This variant has not, to our knowledge, been published in the literature. However, a different nucleotide change at this same position, VHL c.463+4C>G, has been demonstrated to segregate with hemangioblastoma and pheochromocytoma in at least one family and to cause aberrant splicing via RT-PCR (Sexton 2015). VHL c.463+4C>T was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. The cytosine (C) nucleotide that is altered is conserved across species. Based on currently available information, it is unclear whether VHL c.463+4C>T is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000560865 SCV000626905 uncertain significance Erythrocytosis, familial, 2; Von Hippel-Lindau syndrome 2017-08-03 criteria provided, single submitter clinical testing
PreventionGenetics RCV000679042 SCV000805350 likely benign not provided 2018-01-02 criteria provided, single submitter clinical testing

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