ClinVar Miner

Submissions for variant NM_000182.5(HADHA):c.1418C>A (p.Ala473Asp)

gnomAD frequency: 0.00002  dbSNP: rs772166712
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000174666 SCV000226005 uncertain significance not provided 2015-02-23 criteria provided, single submitter clinical testing
Invitae RCV001242839 SCV001415954 uncertain significance Mitochondrial trifunctional protein deficiency; Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency 2022-07-11 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 473 of the HADHA protein (p.Ala473Asp). This variant is present in population databases (rs772166712, gnomAD 0.01%). This missense change has been observed in individual(s) with a positive newborn screening result for HADHA-related disease (Invitae). ClinVar contains an entry for this variant (Variation ID: 194324). 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital RCV003334384 SCV004042672 likely pathogenic Mitochondrial trifunctional protein deficiency 2023-10-12 criteria provided, single submitter clinical testing This variant is identified in homozygous state in a 15 month male with hypothyroidism, hyperparathyroidism and developmental delay. The child developed encephalopathy and liver failure along with raised lactate levels at 15 months. Variant was further confirmed using Sanger sequencing for the homozygosity and was present in both the parents in heterozygous state. This variant has been identified as a very rare variant in gnomAD database with an allele frequency of 0.0016%. Insilico predictions [REVEL:0.96] predicts a damaging nature of this variant. Based on the clinical phenotype and variant characteristics, this variant is considered to be Likely pathogenic.
Natera, Inc. RCV001831998 SCV002076507 uncertain significance Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency 2020-06-18 no assertion criteria provided clinical testing

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