ClinVar Miner

Submissions for variant NM_000183.3(HADHB):c.173A>G (p.Asp58Gly)

gnomAD frequency: 0.00001  dbSNP: rs746076418
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000493351 SCV000583363 uncertain significance not provided 2017-05-31 criteria provided, single submitter clinical testing The D58G variant in the HADHB gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The D58G variant is observed in 2/16512 (0.012%) alleles from individuals of South Asian background and in 2/66736 (0.003%) alleles from individuals of European background, in the ExAC dataset (Lek et al., 2016). The D58G 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 where amino acids with similar properties to Aspartic acid are tolerated across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret D58G as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001208691 SCV001380094 uncertain significance Mitochondrial trifunctional protein deficiency 2021-09-01 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glycine at codon 58 of the HADHB protein (p.Asp58Gly). The aspartic acid residue is moderately conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is present in population databases (rs746076418, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with HADHB-related conditions. ClinVar contains an entry for this variant (Variation ID: 430537). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.

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