Description
The p.Met439Lys (NM_001079803.1 c.1316T>A) variant in GAA has been reported in a t least 10 compound heterozygous individuals with Pompe disease and segregated w ith disease in one affected sibling (Park 2006, Kobayashi 2010, Park 2013, Lee 2 014, Lee 2017 and Park 2017). This variant has also been reported in ClinVar (Va riation ID#371305), as likely pathogenic. In vitro functional studies provide ev idence that the variant impairs enzymatic activity (Flanagan 2009). This varian t has been identified in 6/14,598 of East Asian chromosomes by the Genome Aggreg ation Database (gnomAD, http://gnomAD.broadinstitute.org; dbSNP rs747610090), th ough this frequency is low enough to be consistent with a recessive carrier freq uency. In summary, although additional studies are required to fully establish i ts clinical significance, the p.Met439Lys variant is likely pathogenic for Pompe disease in an autosomal recessive manner based upon observations in affected in dividuals and functional studies. ACMG/AMP Criteria applied: PS3, PM2, PM3, PP5 (Richards 2015)
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | not provided | not provided | not provided | not provided | | 1 | not provided | 1 | not provided |
