ClinVar Miner

Submissions for variant NM_000169.2(GLA):c.196G>C (p.Glu66Gln) (rs104894833)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000728539 SCV000856129 uncertain significance not provided 2017-08-07 criteria provided, single submitter clinical testing
GeneDx RCV000150750 SCV000728500 likely benign not specified 2017-04-05 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000822343 SCV000963143 uncertain significance Fabry disease 2018-09-14 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with glutamine at codon 66 of the GLA protein (p.Glu66Gln). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and glutamine. This variant is present in population databases (rs104894833, ExAC 0.2%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been observed to segregate with late-onset Fabry disease in several families (PMID: 26456105, 11137837) and has been observed in individuals affected with Fabry disease, some of whom had late-onset, mild, or non-classic disease or another variant in GLA (PMID: 1315715, 22874111, 20505683, 7575533, 11137837). This variant has also been observed in individuals affected with hypertrophic cardiomyopathy (PMID: 27160240) and renal failure without accumulation of Gb-3 deposits reported on renal or cardiac biopsy (PMID: 26179544, 23146289). ClinVar contains an entry for this variant (Variation ID: 10723, 163548). Experimental studies have shown that this missense change decreases GLA activity but retains some residual enzyme activity (PMID: 17555407, 18205205, 10845698). 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.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000150750 SCV000198201 uncertain significance not specified 2013-02-11 no assertion criteria provided clinical testing proposed classification - variant undergoing re-assessment, contact laboratory

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