Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Neuberg Centre For Genomic Medicine, |
RCV003337919 | SCV004048351 | pathogenic | Glycogen storage disease, type II | criteria provided, single submitter | clinical testing | The missense variant c.2702T>A (p.Leu901Gln) in GAA gene has been reported in individuals affected with Pompe disease. Experimental studies have shown that p.Leu901Gln variant prevent the conversion of the 110-kDa acid a-glucosidase precursor into processed forms of 95- and 76-kDa (Kroos et al., 2004). The variant has been submitted to the GAA mutation database as Pathogenic/Likely Pathogenic. The p.Leu901Gln variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. The amino acid Leu at position 901 is changed to a Gln changing protein sequence and it might alter its composition and physico-chemical properties. The variant is predicted to be damaging by both SIFT and PolyPhen2. The residue is conserved across species. The amino acid change p.Leu901Gln in GAA is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Pathogenic. |