Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Broad Center for Mendelian Genomics, |
RCV000032678 | SCV001999901 | likely pathogenic | Hyperinsulinemic hypoglycemia, familial, 4 | 2021-11-02 | criteria provided, single submitter | curation | The p.Arg236Ter variant in HADH has been reported in at least 7 individuals with familial hyperinsulinemic hypoglycemia (PMID: 21252247, 19318379), segregated with disease in 2 affected relatives from 1 family (Çayır et al., abstract), and has been identified in 0.008% (2/24952) of African/African American chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs375717077). Although this variant has been seen in the general population in a heterozygous state, its frequency is low enough to be consistent with a recessive carrier frequency. This variant has also been reported in ClinVar (Variation ID#: 39482) and has been interpreted as pathogenic by OMIM. This nonsense variant leads to a premature termination codon at position 236, which is predicted to lead to a truncated or absent protein. Loss of function of the HADH gene is strongly associated to autosomal recessive familial hyperinsulinemic hypoglycemia. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for familial hyperinsulinemic hypoglycemia. ACMG/AMP Criteria applied: PVS1_strong, PM2_supporting, PM3, PP1 (Richards 2015). |
| Revvity Omics, |
RCV001781331 | SCV002023445 | likely pathogenic | not provided | 2022-01-26 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003460539 | SCV004191740 | pathogenic | Deficiency of 3-hydroxyacyl-CoA dehydrogenase | 2023-06-03 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV003460539 | SCV004293213 | pathogenic | Deficiency of 3-hydroxyacyl-CoA dehydrogenase | 2023-10-25 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg236*) in the HADH gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HADH are known to be pathogenic (PMID: 8825408). This variant is present in population databases (rs375717077, gnomAD 0.008%). This premature translational stop signal has been observed in individual(s) with clinical features of medium/short-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (PMID: 19318379, 24686051). ClinVar contains an entry for this variant (Variation ID: 39482). For these reasons, this variant has been classified as Pathogenic. |
| OMIM | RCV000032678 | SCV000056441 | pathogenic | Hyperinsulinemic hypoglycemia, familial, 4 | 2011-03-01 | no assertion criteria provided | literature only |