ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.2069C>T (p.Pro690Leu)

gnomAD frequency: 0.00003  dbSNP: rs532624326
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000485701 SCV000574105 uncertain significance not provided 2017-03-17 criteria provided, single submitter clinical testing The P690L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The P690L variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. However, this substitution occurs at a position that is not conserved, and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.
Invitae RCV000548878 SCV000626541 uncertain significance Glycogen storage disease, type II 2022-09-07 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 690 of the GAA protein (p.Pro690Leu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with GAA-related conditions. ClinVar contains an entry for this variant (Variation ID: 424308). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt GAA protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Genome-Nilou Lab RCV000548878 SCV002027289 uncertain significance Glycogen storage disease, type II 2021-09-05 criteria provided, single submitter clinical testing
Natera, Inc. RCV000548878 SCV001459746 uncertain significance Glycogen storage disease, type II 2020-09-16 no assertion criteria provided clinical testing

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