Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000589535 | SCV000695742 | likely pathogenic | Fabry disease | 2016-12-20 | criteria provided, single submitter | clinical testing | Variant summary: The GLA c.59_72dupCCCTCGTTTCCTGG (p.Asp25Profs) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.59_84del26, p.Ala20Glyfs). One in silico tool predicts a damaging outcome for this variant. This variant is absent in 87697 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as likely pathogenic. |
Eurofins Ntd Llc |
RCV000727496 | SCV000709138 | pathogenic | not provided | 2017-06-06 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV000589535 | SCV002054465 | pathogenic | Fabry disease | 2021-07-15 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000589535 | SCV002187496 | pathogenic | Fabry disease | 2021-08-23 | 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: 495695). This variant has not been reported in the literature in individuals affected with GLA-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Asp25Profs*101) 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). |