ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.2105G>T (p.Arg702Leu) (rs398123172)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000174831 SCV000226206 likely pathogenic not provided 2013-06-19 criteria provided, single submitter clinical testing
Invitae RCV000792061 SCV000931333 pathogenic Glycogen storage disease, type II 2018-09-19 criteria provided, single submitter clinical testing This sequence change replaces arginine with leucine at codon 702 of the GAA protein (p.Arg702Leu). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in combination with another GAA variant in individuals affected with infantile onset Pompe disease (PMID: 29122469, 27344650, 22252923). ClinVar contains an entry for this variant (Variation ID: 92472). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Arg702 amino acid residue in GAA. Other variants that disrupt this residue have been observed in affected individuals (PMID: 18211760, 18425781, 26310554), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

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