ClinVar Miner

Submissions for variant NM_175914.4(HNF4A):c.187C>T (p.Arg63Trp) (rs587777732)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory,University of Chicago RCV000193614 SCV000247562 pathogenic Hyperinsulinemia 2015-02-09 criteria provided, single submitter clinical testing
GeneDx RCV000255966 SCV000322351 pathogenic not provided 2017-01-10 criteria provided, single submitter clinical testing The R63W variant in the HNF4A gene has been reported previously using alternate nomenclature R76W in association with congenital hyperinsulinism, macrosomia, and renal Fanconi syndrome (Stanescu et al., 2012; Hamilton et al., 2014; Numakura et al., 2015). The R63W variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R63W variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. A missense variant in the same residue (R63Q) has been previously reported in association with maturity-onset diabetes of the young (Colclough et al., 2013). We interpret R63W as a pathogenic variant.
Genetic Services Laboratory,University of Chicago RCV000502760 SCV000595151 pathogenic Hyperinsulinism due to HNF4A deficiency 2017-04-27 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763446 SCV000894217 pathogenic Maturity-onset diabetes of the young, type 1; Type 2 diabetes mellitus; Fanconi renotubular syndrome 4 with maturity-onset diabetes of the young 2018-10-31 criteria provided, single submitter clinical testing
Baylor Genetics RCV000850560 SCV000992775 pathogenic Maturity-onset diabetes of the young, type 1; Fanconi renotubular syndrome 4 with maturity-onset diabetes of the young 2017-12-31 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000255966 SCV001475907 pathogenic not provided 2019-12-13 criteria provided, single submitter clinical testing Not found in the total gnomAD dataset, and the data is high quality. Predicted to have a damaging effect on the protein. Found in multiple individuals with expected phenotype for this gene. Segregation with disease, and data include affected and unaffected individuals from multiple families. One de novo case with parental identity confirmed plus 2 unconfirmed cases.
OMIM RCV000144170 SCV000189247 pathogenic Fanconi renotubular syndrome 4 with maturity-onset diabetes of the young 2014-03-01 no assertion criteria provided literature only

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