ClinVar Miner

Submissions for variant NM_000169.3(GLA):c.154dup (p.Cys52fs)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002308607 SCV002600549 likely pathogenic Fabry disease 2022-10-18 criteria provided, single submitter clinical testing Variant summary: GLA c.154dupT (p.Cys52LeufsX4) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory and associated with Fabry disease in HGMD. The variant was absent in 183425 control chromosomes. To our knowledge, no occurrence of c.154dupT in individuals affected with Fabry Disease and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Revvity Omics, Revvity RCV003491080 SCV004238219 likely pathogenic not provided 2023-06-14 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002308607 SCV004274720 pathogenic Fabry disease 2023-06-19 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1723331). This variant has not been reported in the literature in individuals affected with GLA-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Cys52Leufs*4) in the GLA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GLA are known to be pathogenic (PMID: 10666480, 12175777).

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