ClinVar Miner

Submissions for variant NM_000182.5(HADHA):c.2027G>A (p.Arg676His)

dbSNP: rs1204190984
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001220239 SCV001392219 pathogenic Mitochondrial trifunctional protein deficiency; Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency 2024-04-15 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 676 of the HADHA protein (p.Arg676His). This variant is present in population databases (no rsID available, gnomAD 0.007%). This missense change has been observed in individual(s) with HADHA-related conditions (PMID: 10352164, 21549624, 26109258; Invitae). This variant is also known as Arg640His. ClinVar contains an entry for this variant (Variation ID: 948895). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt HADHA protein function with a positive predictive value of 80%. This variant disrupts the p.Arg676 amino acid residue in HADHA. Other variant(s) that disrupt this residue have been observed in individuals with HADHA-related conditions (PMID: 24305961), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001587243 SCV001826883 likely pathogenic not provided 2019-10-14 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 29915090, 15902556, 21549624, 10352164)
Baylor Genetics RCV003469379 SCV004191792 likely pathogenic Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency 2024-03-02 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005021523 SCV005651669 likely pathogenic Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency; Mitochondrial trifunctional protein deficiency 1 2024-04-03 criteria provided, single submitter clinical testing

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