ClinVar Miner

Submissions for variant NM_000182.5(HADHA):c.2114T>A (p.Val705Asp)

gnomAD frequency: 0.00002  dbSNP: rs1240187200
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521619 SCV000618078 likely pathogenic not provided 2017-09-06 criteria provided, single submitter clinical testing The V705D variant has previously been reported as homozygous in an individual with mitochondrial trifunctional protein deficiency (Djouadi et al., 2015). This individual had significantly reduced long chain fatty acid oxidation in fibroblasts (Djouadi et al., 2015). The V705D variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The V705D variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. In summary, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Counsyl RCV000674004 SCV000799273 uncertain significance Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency 2018-04-11 criteria provided, single submitter clinical testing
Baylor Genetics RCV000674004 SCV004191751 likely pathogenic Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency 2023-10-13 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004701592 SCV005202625 uncertain significance not specified 2024-07-11 criteria provided, single submitter clinical testing Variant summary: HADHA c.2114T>A (p.Val705Asp) 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 was absent in 251208 control chromosomes. c.2114T>A has been reported in the literature in individuals affected with Mitochondrial Trifunctional Protein Deficiency (Djouadi_2016). 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. The following publication have been ascertained in the context of this evaluation (PMID: 26109258). ClinVar contains an entry for this variant (Variation ID: 449719). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
Natera, Inc. RCV000674004 SCV002076493 likely pathogenic Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency 2020-08-17 no assertion criteria provided clinical testing

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