ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.1082C>T (p.Pro361Leu) (rs755253527)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Claritas Genomics RCV000464818 SCV000503002 pathogenic Glycogen storage disease, type II 2016-10-06 criteria provided, single submitter clinical testing The c.1082C>T (p.Pro361Leu) missense variant is previously reported in the literature and is expected to be causative of disease. This variant has been reported in multiple affected individuals across multiple studies. This variant is classified as Class B, which means potentially less severe (Kroos M et al. Hum Mutat. 2012;33(8):1161-5). Patients with this class of variant are CRIM-positive. This variant involves a highly conserved nucleotide and amino acid. PolyPhen-2, SIFT, and MutationTaster all predict this variant to be deleterious.
Invitae RCV000464818 SCV000948715 pathogenic Glycogen storage disease, type II 2018-11-20 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 361 of the GAA protein (p.Pro361Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs755253527, ExAC 0.02%). This variant has been observed to be homozygous or in combination with another GAA variant in individuals affected with Pompe disease (PMID: 12601120, 16917947, 25213570, 27344650, 30023291). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 403712). Experimental studies have shown that this missense change produces no GAA enzyme activity in vitro (PMID: 12601120). For these reasons, this variant has been classified as Pathogenic.

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