ClinVar Miner

Submissions for variant NM_000182.5(HADHA):c.2026C>T (p.Arg676Cys)

gnomAD frequency: 0.00001  dbSNP: rs771028541
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001376804 SCV001573975 pathogenic Mitochondrial trifunctional protein deficiency; Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency 2023-12-03 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 676 of the HADHA protein (p.Arg676Cys). This variant is present in population databases (rs771028541, gnomAD 0.01%). This missense change has been observed in individual(s) with 3-hydroxyacyl-CoA dehydrogenase deficiency (PMID: 10352164). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as p.Arg640Cys. ClinVar contains an entry for this variant (Variation ID: 1065948). 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 determined to be pathogenic (PMID: 10352164, 21549624, 26109258; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV001376804 SCV002792025 likely pathogenic Mitochondrial trifunctional protein deficiency; Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency 2021-10-10 criteria provided, single submitter clinical testing
Baylor Genetics RCV003469618 SCV004191782 likely pathogenic Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency 2023-12-14 criteria provided, single submitter clinical testing

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