ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.181C>G (p.Pro61Ala) (rs113612866)

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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 RCV000562742 SCV000664708 uncertain significance Hereditary cancer-predisposing syndrome 2017-01-03 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbsnp, esp, 1000 genomes),Insufficient evidence
Invitae RCV000233504 SCV000285490 uncertain significance Erythrocytosis, familial, 2; Von Hippel-Lindau syndrome 2016-01-25 criteria provided, single submitter clinical testing This sequence change replaces proline with alanine at codon 61 of the VHL protein (p.Pro61Ala). The proline residue is highly conserved and there is a small physicochemical difference between proline and alanine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a VHL-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. In summary, this is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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