ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.2237G>C (p.Trp746Ser) (rs752921215)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000626060 SCV000795205 likely pathogenic Glycogen storage disease, type II 2017-11-08 criteria provided, single submitter clinical testing
Genomic Research Center,Shahid Beheshti University of Medical Sciences RCV000626060 SCV000746682 likely pathogenic Glycogen storage disease, type II 2017-12-18 criteria provided, single submitter clinical testing
Invitae RCV000626060 SCV000950050 pathogenic Glycogen storage disease, type II 2018-12-20 criteria provided, single submitter clinical testing This sequence change replaces tryptophan with serine at codon 746 of the GAA protein (p.Trp746Ser). The tryptophan residue is highly conserved and there is a large physicochemical difference between tryptophan and serine. This variant is present in population databases (rs752921215, ExAC 0.04%). This variant has been observed in several individuals affected with Pompe disease (PMID: 22081099, 18425781). ClinVar contains an entry for this variant (Variation ID: 188484). Experimental studies have shown that this missense change causes a mild disruption of GAA protein function (PMID: 23430493). This variant disrupts the p.Trp746 amino acid residue in GAA. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 18458862, 21757382, 21232767, 23430493, 25526786, 27099502, 25093132), 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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