ClinVar Miner

Submissions for variant NM_000169.2(GLA):c.724A>G (p.Ile242Val) (rs397515873)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Albrecht-Kossel-Institute,Medical University Rostock RCV000209315 SCV000246067 pathogenic Fabry disease 2014-01-01 no assertion criteria provided research
Albrecht-Kossel-Institute,Medical University Rostock RCV000209695 SCV000246068 drug response Deoxygalactonojirimycin response 2014-01-01 no assertion criteria provided research
GeneDx RCV000441727 SCV000513154 uncertain significance not provided 2017-01-05 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the GLA gene. The I242V variant has been reported in one patient referred for Fabry disease testing who had slightly elevated levels of Globotriaosylceramide (Lukas et al., 2016). This variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. However, the I242V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved across species and where Valine is the wild type in several species. In silico analysis predicts this variant likely does not alter the protein structure/function. Finally, while missense variants affecting the same residue (I242N, I242F) have been reported in the Human Gene Mutation Database in association with Fabry disease (Stenson et al., 2014), the pathogencity of these variants has not been definitively determined.

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