ClinVar Miner

Submissions for variant NM_000169.3(GLA):c.894T>A (p.Asn298Lys)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV001193068 SCV001361650 pathogenic Fabry disease 2019-07-31 criteria provided, single submitter clinical testing Variant summary: GLA c.894T>A (p.N298K) results in a non-conservative amino acid change located in the Aldolase-type TIM barrel domain (IPR013785) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 183457 control chromosomes (gnomAD). The variant, in most of the reported cases described at the protein level as p.N298K (with unspecified nucleotide level change), has been reported in the literature in individuals affected with Fabry Disease (Ashton-Prolla_2000, Sadick_2007, Cheung_2012, Boyd_2013, Sigmundsdottir_2014). These data indicate that the variant may be associated with disease. At least two publications reported alpha-galactosidase activity values for the variant protein and demonstrated significantly decreased residual activities (i.e. less than 10% of normal) (Sadick_2007, Benjamin_2017). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.

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