ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.558A>C (p.Glu186Asp)

dbSNP: rs587778744
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001038969 SCV001202474 uncertain significance Chuvash polycythemia; Von Hippel-Lindau syndrome 2023-03-16 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The aspartic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 135407). This variant has not been reported in the literature in individuals affected with VHL-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 186 of the VHL protein (p.Glu186Asp).
Ambry Genetics RCV003162559 SCV003858792 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-01 criteria provided, single submitter clinical testing The p.E186D variant (also known as c.558A>C), located in coding exon 3 of the VHL gene, results from an A to C substitution at nucleotide position 558. The glutamic acid at codon 186 is replaced by aspartic acid, an amino acid with highly similar properties. This variant was identified in a cohort of 681 ancestrally diverse, healthy subjects (Bodian DL et al. PLoS One, 2014 Apr;9:e94554). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
ITMI RCV000122261 SCV000086486 not provided not specified 2013-09-19 no assertion provided reference population

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