ClinVar Miner

Submissions for variant NM_005327.5(HADH):c.662G>A (p.Arg221His) (rs76476980)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Personalized Diabetes Medicine Program,University of Maryland School of Medicine RCV000445511 SCV000537024 uncertain significance Monogenic diabetes 2018-01-12 criteria provided, single submitter research ACMG criteria: PP3 (10 predictors), BS2 (27 cases and 24 controls in type2diabetesgenetics.org)=VUS NOTE: GeneDx also calls VUS
GeneDx RCV000521350 SCV000617017 uncertain significance not provided 2015-04-01 criteria provided, single submitter clinical testing The R221H variant in the HADH gene has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. The NHLBI ESP Exome Sequencing Project reports R221H was observed in 42/4406 alleles (0.95%) from individuals of African American background, indicating it may be a rare variant in this population. The R221H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. A missense pathogenic variant in a nearby residues (Y226H) has been reported in the Human Gene Mutation Database in association with hyperinsulinemic hypoglycemia (Stenson et al., 2014), supporting the functional importance of this region of the protein. We interpret R221H as a variant of unknown significance.
Fulgent Genetics,Fulgent Genetics RCV000764524 SCV000895607 uncertain significance Deficiency of 3-hydroxyacyl-CoA dehydrogenase; Hyperinsulinemic hypoglycemia, familial, 4 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV001084606 SCV001013401 benign Deficiency of 3-hydroxyacyl-CoA dehydrogenase 2019-12-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001084606 SCV001306522 benign Deficiency of 3-hydroxyacyl-CoA dehydrogenase 2017-06-26 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Illumina Clinical Services Laboratory,Illumina RCV001145824 SCV001306523 benign Hyperinsulinemic hypoglycemia, familial, 4 2017-06-26 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.