ClinVar Miner

Submissions for variant NM_000108.5(DLD):c.161A>G (p.Tyr54Cys)

gnomAD frequency: 0.00003  dbSNP: rs763303046
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000484591 SCV000574056 likely pathogenic not provided 2017-04-03 criteria provided, single submitter clinical testing The Y54C variant in the DLD gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The Y54C variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The Y54C 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. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret Y54C as a likely pathogenic variant.
Invitae RCV000675101 SCV002195863 uncertain significance Pyruvate dehydrogenase E3 deficiency 2021-06-28 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 54 of the DLD protein (p.Tyr54Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with DLD-related conditions. ClinVar contains an entry for this variant (Variation ID: 424265). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Counsyl RCV000675101 SCV000800637 uncertain significance Pyruvate dehydrogenase E3 deficiency 2017-12-13 no assertion criteria provided clinical testing

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