ClinVar Miner

Submissions for variant NM_000169.2(GLA):c.485G>A (p.Trp162Ter) (rs727504350)

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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 RCV000723475 SCV000228802 pathogenic not provided 2015-04-27 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000176999 SCV000695741 pathogenic Fabry disease 2016-12-14 criteria provided, single submitter clinical testing Variant summary: The GLA c.485G>A (p.Trp162X) variant results in a premature termination codon, predicted to cause a truncated or absent GLA protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant of interest was not observed in controls (ExAC, 1000 Gs, or ESP) and has been reported in multiple affected individuals including one family that female individuals in the family carrying the variant showed mild features including low levels of GLA activity. In addition, males carrying the variant of interest showed no GLA activity. In addition, a clinical diagnostic laboratory cites the variant as "pathogenic." Therefore, the variant of interest has been classified as "pathogenic."
Invitae RCV000176999 SCV000935550 pathogenic Fabry disease 2018-11-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp162*) in the GLA gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with Fabry disease (PMID: 10649504, 11668641). ClinVar contains an entry for this variant (Variation ID: 196226). Experimental studies have shown that this nonsense change abolishes enzyme activity (PMID: 26415523). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Loss-of-function variants in GLA are known to be pathogenic (PMID: 10666480, 12175777). For these reasons, this variant has been classified as Pathogenic.

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