ClinVar Miner

Submissions for variant NM_005327.5(HADH):c.275T>G (p.Phe92Cys) (rs61735992)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory,University of Chicago RCV000193662 SCV000247539 uncertain significance not specified 2015-02-24 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000224208 SCV000281183 likely benign not provided 2015-12-23 criteria provided, single submitter clinical testing Converted during submission to Likely benign.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000224208 SCV000493328 uncertain significance not provided 2018-01-01 criteria provided, single submitter clinical testing
GeneDx RCV000224208 SCV000617016 uncertain significance not provided 2017-05-25 criteria provided, single submitter clinical testing The F92C variant in the HADH gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The F92C variant is observed in 117/16512 (0.71%) alleles from individuals of South Asian background, and in 457/66740 (0.69%) alleles from individuals of European background, including 7 unrelated homozygous individuals in an external variant database (Lek et al., 2016). The F92C 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. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret F92C as a variant of uncertain significance.
Personalized Diabetes Medicine Program,University of Maryland School of Medicine RCV000664099 SCV000787551 benign Monogenic diabetes 2019-01-25 criteria provided, single submitter research ACMG criteria: PP3 (REVEL=0.71 + 8 predictors; not using BP4/2 predictors), BS2 (78 cases and 88 controls in type2diabetesgenetics.org; 8 homozygotes in gnomAD), BS1 (0.5% overall MAF in gnomAD)= benign
Invitae RCV001084975 SCV001012272 likely benign Deficiency of 3-hydroxyacyl-CoA dehydrogenase 2019-12-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001084975 SCV001304491 likely benign Deficiency of 3-hydroxyacyl-CoA dehydrogenase 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Clinical Services Laboratory,Illumina RCV001143927 SCV001304492 uncertain significance Hyperinsulinemic hypoglycemia, familial, 4 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

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