Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000778663 | SCV000914996 | uncertain significance | NAGA-Related Disorders | 2018-08-30 | criteria provided, single submitter | clinical testing | The NAGA c.986G>A (p.Arg329Gln) missense variant has been reported in a homozygous state in one individual with Kanzaki disease (Kodama et al. 2001). The α-N-acetylgalactosaminidase enzyme activity in the individual's plasma was 0.77% of normal. Further evaluation of this individual showed that the ratio of urinary excreted GalNAcα1-O-Ser to GalNAcα1-O-Thr was 2:10, indicating that the p.Arg329Gln variant retains some ability to catalyze GalNAcα1-O-Ser (Kanekura et al. 2005). Homology modeling suggests that the p.Arg329Gln variant disrupts hydrogen bonds at the interface between domains I and II, which decreases protein stability and may cause a folding defect (Sakuraba et al. 2004). Control data are unavailable for this variant, which is reported at a frequency of 0.00006 in the European (non-Finnish) population of the Exome Aggregation Consortium. Based on the evidence, the p.Arg329Gln is classified as a variant of unknown significance but suspicious for pathogenicity for NAGA-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
OMIM | RCV000019796 | SCV000040094 | pathogenic | Alpha-N-acetylgalactosaminidase deficiency type 2 | 2001-02-01 | no assertion criteria provided | literature only |