ClinVar Miner

Submissions for variant NM_000262.3(NAGA):c.986G>A (p.Arg329Gln) (rs121434533)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina 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

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