ClinVar Miner

Submissions for variant NM_000169.2(GLA):c.247G>A (p.Asp83Asn) (rs782722577)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000471970 SCV000543775 uncertain significance Fabry disease 2018-09-17 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 83 of the GLA protein (p.Asp83Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs782722577, ExAC 0.004%). This variant has been observed in two females with with reduced alpha-galactosidase activity on screening tests (PMID: 24365053, 26070511). However, on follow up studies, one female and her unaffected brother who was hemizygous for this variant, were both confirmed to have normal plasma and leukocyte alpha-galactosidase activity (PMID: 26070511). In addition, this variant has been reported in two individuals affected with stroke (PMID: 23935525, 23306324). One of them was confirmed with Fabry disease and had a significantly reduced alpha-galactosidase activity and increase of biochemical markers (PMID: 23306324)]. Experimental studies have shown that this missense change results in 69% of wild type enzyme activity (PMID: 27657681). 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.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000596614 SCV000703121 uncertain significance not provided 2016-11-14 criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000471970 SCV000734725 uncertain significance Fabry disease no assertion criteria provided clinical testing
Stanford Center for Inherited Cardiovascular Disease, Stanford University RCV000596614 SCV000925085 uncertain significance not provided 2017-09-22 no assertion criteria provided provider interpretation

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