ClinVar Miner

Submissions for variant NM_000169.2(GLA):c.707G>A (p.Trp236Ter) (rs879254022)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000235716 SCV000293199 pathogenic not provided 2015-09-24 criteria provided, single submitter clinical testing The W236X nonsense variant in the GLA gene has been reported previously in association with Fabry disease (Jojart et al., 2009; Germain et al., 2002), and its presence is consistent with the diagnosis in the patient. This mutation is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Approximately 60-70% of females with a single GLA mutation have some disease manifestations, and 10% of these individuals present with a disease severity that is similar to that of affected males (Bennett et al., 2002).
Invitae RCV000692369 SCV000820189 pathogenic Fabry disease 2018-09-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp236*) 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 reported in individuals with classic Fabry disease (PMID: 12428061, 27560961). ClinVar contains an entry for this variant (Variation ID: 245967). 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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