ClinVar Miner

Submissions for variant NM_000169.2(GLA):c.791A>T (p.Asp264Val) (rs28935486)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724649 SCV000700796 pathogenic not provided 2018-09-12 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000011480 SCV000695746 pathogenic Fabry disease 2016-12-21 criteria provided, single submitter clinical testing Variant summary: The GLA c.791A>T (p.Asp264Val) variant involves the alteration of a conserved nucleotide and is located in aldolase-type TIM barrel and/or glycoside hydrolase superfamily domain (InterPro) close to the active site of the protein (Lukas_2013). 5/5 in silico tools predict a damaging outcome for this variant. In vitro and in vivo cell-based assays show that this variant abrogates the enzymatic activity (Benjamin_2009, Lukas_2013, Wu_2011) which not being responsive to pharmacological chaperone therapy. This variant is absent in approximately 87702 control chromosomes from ExAC. In literature, this variant has been detected in at least three unrelated patients with classic Fabry disease (Eng_1993, Brown_1997, Shabbeer_2005, Wu_2011). Another missense change at the same residue p.Asp264Tyr is functionally defective (Lukas_2013) and is evaluated as pathogenic by our laboratory, further supporting the importance of Asp264 codon and pathogenicity of the variant of interst. Multiple clinical diagnostic reputable databases have classified this variant as pathogenic. Taken together, this variant is classified as Pathogenic.
OMIM RCV000011480 SCV000031712 pathogenic Fabry disease 1993-12-01 no assertion criteria provided literature only

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