ClinVar Miner

Submissions for variant NM_000410.4(HFE):c.829G>A (p.Glu277Lys)

gnomAD frequency: 0.00081  dbSNP: rs140080192
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000473336 SCV000461886 uncertain significance Hemochromatosis type 1 2016-08-03 criteria provided, single submitter clinical testing The HFE c.829G>A (p.Glu277Lys) variant is a missense variant that has been reported in at least one study, in which it was found in a compound heterozygous state with a second missense variant in one Portuguese individual with suspected hereditary hemochromatosis (Mendes et al. 2009). Family studies showed that the individual's brother had the same genotype and high serum ferritin levels. Functional studies by Silva et al. (2012) suggest that the p.Glu277Lys variant affects splicing, protein cell surface presentation and protein processing. The p.Glu277Lys variant was absent from 50 controls (Bradbury et al. 2000) and is reported at a frequency of 0.02459 in the South Asian population of the Exome Aggregation Consortium. This allele frequency is high but is consistent with the disease prevalence, reduced penetrance and mild phenotype. The evidence for this variant is limited. The p.Glu277Lys variant is therefore classified as a variant of unknown significance but suspicious for pathogenicity for hereditary hemochromatosis. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Labcorp Genetics (formerly Invitae), Labcorp RCV001084109 SCV000557781 likely benign Hereditary hemochromatosis 2024-01-31 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000727614 SCV000854872 uncertain significance not provided 2017-10-10 criteria provided, single submitter clinical testing
GeneDx RCV000727614 SCV001829973 benign not provided 2020-05-18 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 27153395, 27884173, 10612845, 22624560, 18762941)
CeGaT Center for Human Genetics Tuebingen RCV000727614 SCV004700295 benign not provided 2024-07-01 criteria provided, single submitter clinical testing HFE: BP4, BS1, BS2
Mayo Clinic Laboratories, Mayo Clinic RCV000727614 SCV005412016 uncertain significance not provided 2023-10-13 criteria provided, single submitter clinical testing BA1, BS2, BP4

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