Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003050638 | SCV003445377 | pathogenic | Fabry disease | 2023-08-16 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Cys142*) 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). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 2138667). This premature translational stop signal has been observed in individual(s) with Fabry disease (PMID: 10666480). This variant is not present in population databases (gnomAD no frequency). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003050638 | SCV004020484 | pathogenic | Fabry disease | 2023-06-05 | criteria provided, single submitter | clinical testing | Variant summary: GLA c.426C>A (p.Cys142X) 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. The variant was absent in 183470 control chromosomes (gnomAD, v2.1). c.426C>A has been reported in the literature in individuals affected with Fabry Disease, including two hemizygous affected brothers (e.g., Ries_2005). These data indicate that the variant is likely to be associated with disease. The following publication was ascertained in the context of this evaluation (PMID: 15713906). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |