Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001260301 | SCV001437223 | pathogenic | Fabry disease | 2020-09-01 | criteria provided, single submitter | clinical testing | Variant summary: GLA c.350T>G (p.Ile117Ser) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 183291 control chromosomes. c.350T>G has been reported in the literature in multiple individuals affected with adult/late-onset Fabry Disease (example, Stepien_2017, Germain_2020) and in Fabry patients with predominant renal manifestations (example McCloskey_2018). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal alpha Gal-A enzyme activity (Benjamin_2016). 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 pathogenic. |