Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mendelics | RCV000987462 | SCV001136757 | pathogenic | Deficiency of 3-hydroxyacyl-CoA dehydrogenase | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Broad Center for Mendelian Genomics, |
RCV001766804 | SCV001999899 | likely pathogenic | Hyperinsulinemic hypoglycemia, familial, 4 | 2021-11-02 | criteria provided, single submitter | curation | The p.Ser196fs variant in HADH has been reported in 3 individuals with familial hyperinsulinemic hypoglycemia (PMID: 21347589), segregated with disease in 2 affected relatives from 1 family (PMID: 21347589), and has been identified in 0.003% (1/34592) of Latino/Admixed American chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs745727504). 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#: 802083) and has been interpreted as pathogenic by Mendelics. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 196 and leads to a premature termination codon 3 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the HADH gene is strongly associated to familial hyperinsulinemic hypoglycemia . In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for autosomal recessive familial hyperinsulinemic hypoglycemia. ACMG/AMP Criteria applied: PVS1_strong, PM3_supporting, PM2_supporting, PP1 (Richards 2015). |
| Invitae | RCV000987462 | SCV002228035 | pathogenic | Deficiency of 3-hydroxyacyl-CoA dehydrogenase | 2023-12-19 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser196Phefs*3) 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 (rs745727504, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with medium/short-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (PMID: 21347589). ClinVar contains an entry for this variant (Variation ID: 802083). For these reasons, this variant has been classified as Pathogenic. |
| Clinical Genomics, |
RCV001766804 | SCV003915661 | likely risk allele | Hyperinsulinemic hypoglycemia, familial, 4 | 2024-02-14 | criteria provided, single submitter | research | Potent mutations in HADH gene are associated with congenital hyperinsulinism, which leads to recurrent hypoglycemia. The condition is exacerbated by stress, fasting or excessive dietary protein. May respond well to diazoxide. However, the role of this particular variant rs745727504 in congenital hyperinsulinism is yet to be ascertained. This variant is a potent high-impact, deletion, frameshift variant. Though this is classified as Likely pathogenic (PVS1) as per ACMG guidelines, there is no sufficient variant evidence in the literature to classify it under the same. Hence this variant has been reclassified as a Likely risk allele as per the recent scientific evidence. |
| Baylor Genetics | RCV000987462 | SCV004191743 | pathogenic | Deficiency of 3-hydroxyacyl-CoA dehydrogenase | 2023-03-13 | criteria provided, single submitter | clinical testing |