Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000673271 | SCV000798454 | uncertain significance | Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency | 2018-03-18 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002298732 | SCV002598573 | uncertain significance | not specified | 2022-09-26 | criteria provided, single submitter | clinical testing | Variant summary: HADHA c.1828C>G (p.Arg610Gly) results in a non-conservative amino acid change located in the 3-hydroxyacyl-CoA dehydrogenase, C-terminal (IPR006108) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251476 control chromosomes. c.1828C>G has been reported in the literature as a compound heterozygous genotype in a clinically and metabolically diagnosed patient affected with Long Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency who carried the common pathogenic variant c.1528G>C on the second allele (Sykut-Cegielska_2011). Additionally, the variant was reported along with a novel HADHA variant (c.2281T>G) in three siblings diagnosed with later-onset, somewhat mild MTP (4-9 years old) (Grnert_2021, Grnert_2022). In these siblings, HADHB was not tested. These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS - possibly pathogenic. |