ClinVar Miner

Submissions for variant NM_002225.5(IVD):c.1232G>A (p.Arg411Gln) (rs143348838)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000523707 SCV000619267 likely pathogenic not provided 2017-07-13 criteria provided, single submitter clinical testing The R414Q variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R414Q variant is observed in 1/11578 (0.01%) alleles from individuals of Latino background, in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R414Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. R414 is an important residue for stability and activity of the isovaleryl-CoA dehydrogenase enzyme, and a different missense change at this position (R414L) has been reported, using alternate nomenclature, to be associated with 7% of wild-type enzyme activity when expressed in E. coli (Mohsen et al. 1998). Furthermore, in silico analysis predicts that the R414Q variant is probably damaging to the protein structure/function. In summary, we interpret the R414Q variant as likely pathogenic; however, the possibility that it is benign cannot be excluded.
Counsyl RCV000674039 SCV000799310 uncertain significance Isovaleryl-CoA dehydrogenase deficiency 2018-04-09 criteria provided, single submitter clinical testing

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