ClinVar Miner

Submissions for variant NM_002225.5(IVD):c.1066G>A (p.Asp356Asn) (rs398123679)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000417380 SCV000111885 uncertain significance not provided 2013-04-10 criteria provided, single submitter clinical testing
GeneDx RCV000417380 SCV000238935 likely pathogenic not provided 2017-06-22 criteria provided, single submitter clinical testing The D359N variant has not been published as a pathogenic variant, nor has it been reported as abenign variant to our knowledge. The D359N variant is not observed in large population cohorts (Leket al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The D359N variant is asemi-conservative amino acid substitution, which may impact secondary protein structure as theseresidues differ in some properties. This substitution occurs at a position that is conserved acrossspecies. In silico analysis predicts this variant is probably damaging to the protein structure/function.In summary, this variant is likely pathogenic.
Invitae RCV000557255 SCV000631881 likely pathogenic Isovaleryl-CoA dehydrogenase deficiency 2019-05-29 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 359 of the IVD protein (p.Asp359Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has been observed as homozygous in individuals affected with isovaleric acidemia (Invitae). ClinVar contains an entry for this variant (Variation ID: 94050). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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