ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.18G>T (p.Glu6Asp) (rs1004620245)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000459599 SCV000553415 uncertain significance Erythrocytosis, familial, 2; Von Hippel-Lindau syndrome 2016-11-21 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with aspartic acid at codon 6 of the VHL protein (p.Glu6Asp). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. While this variant is not present in population databases (no rsID), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant 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 tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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