ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.1978C>T (p.Arg660Cys) (rs759518659)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000674901 SCV000800311 likely pathogenic Glycogen storage disease, type II 2018-05-31 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000674901 SCV000919375 pathogenic Glycogen storage disease, type II 2018-02-08 criteria provided, single submitter clinical testing Variant summary: GAA c.1978C>T (p.Arg660Cys) results in a non-conservative amino acid change located in the Catalytic GH31 domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in 10%-<30% of normal activity, potentially, due to the change affecting maturation process (Flanagan_2009; Palmer_2007). The variant allele was found at a frequency of 1.1e-05 in 1/91962 control chromosomes in ExAC dataset. The c.1978C>T has been reported in the literature in multiple individuals affected with Glycogen Storage Disease, Type 2 (Pompe Disease). These data indicate that the variant is very likely to be associated with disease. In addition, another alteration of the same codon, R660H, has been reported as "Pathogenic" for Pompe disease. 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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