ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.307T>G (p.Cys103Gly) (rs398123174)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000078179 SCV000227028 pathogenic not provided 2012-11-14 criteria provided, single submitter clinical testing
GeneDx RCV000078179 SCV000322396 pathogenic not provided 2018-07-03 criteria provided, single submitter clinical testing The C103G variant in the GAA gene has been reported previously in multiple unrelated individuals with Pompe disease (Hermans et al., 2004; Joshi et al., 2008; Pittis et al., 2008). The C103G variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The C103G variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In vitro expression analysis of C103G indicates that this variant leads to approximately 98% loss of lysosomal alpha glucosidase activity (Hermans et al., 2004). We interpret C103G as a pathogenic variant.
Invitae RCV000811478 SCV000951746 pathogenic Glycogen storage disease, type II 2018-12-26 criteria provided, single submitter clinical testing This sequence change replaces cysteine with glycine at codon 103 of the GAA protein (p.Cys103Gly). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in combination with another GAA variant in several individuals affected with glycogen storage disease type II (PMID: 21109266, 29181627, 18429042, 18607768, 14695532, 24158270). ClinVar contains an entry for this variant (Variation ID: 92483). This variant has been reported to affect GAA protein function (PMID: 14695532). For these reasons, this variant has been classified as Pathogenic.

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