ClinVar Miner

Submissions for variant NM_000410.4(HFE):c.496A>G (p.Lys166Glu)

gnomAD frequency: 0.00023  dbSNP: rs144170531
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001555930 SCV001777423 uncertain significance not provided 2021-01-27 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001882638 SCV002188446 uncertain significance Hereditary hemochromatosis 2021-08-31 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamic acid at codon 166 of the HFE protein (p.Lys166Glu). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is present in population databases (rs144170531, ExAC 0.09%). This variant has not been reported in the literature in individuals affected with HFE-related conditions. 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. 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.
Genome-Nilou Lab RCV003127991 SCV003802644 uncertain significance Hemochromatosis type 1 2023-02-08 criteria provided, single submitter clinical testing

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