ClinVar Miner

Submissions for variant NM_000169.2(GLA):c.679C>T (p.Arg227Ter) (rs104894841)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV000011479 SCV000188767 pathogenic Fabry disease 2014-01-30 no assertion criteria provided clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000157897 SCV000110133 pathogenic not provided 2018-05-08 criteria provided, single submitter clinical testing
GeneDx RCV000157897 SCV000207828 pathogenic not provided 2017-10-24 criteria provided, single submitter clinical testing The R227X nonsense mutation in the GLA gene has been reported previously in association with Fabry disease (Davies et al., 1993; Shimotori et al., 2007). 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).The variant is found in GLA panel(s).
Invitae RCV000011479 SCV000965451 pathogenic Fabry disease 2018-12-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg227*) 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 affected with Fabry disease including one female who is also affected with hypertrophic cardiomyopathy (PMID: 26047621, 25439755, 8395937, 18205205). ClinVar contains an entry for this variant (Variation ID: 10733). 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.
OMIM RCV000011479 SCV000031711 pathogenic Fabry disease 1993-12-01 no assertion criteria provided literature only

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