Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000781425 | SCV000919443 | pathogenic | Fabry disease | 2018-08-21 | criteria provided, single submitter | clinical testing | Variant summary: GLA c.1021G>A (p.Glu341Lys) results in a conservative amino acid change located in the Alpha galactosidase A, C-terminal beta-sandwich domain of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. Other variants at this codon have been reported in the litertature in association with Fabry Disease (E341G, E341D). The variant was absent in 178226 control chromosomes. c.1021G>A has been reported in the literature in multiple individuals affected with Fabry Disease, inlcuding a large family with segregation data (Beyer_1999). These data indicate that the variant is very likely to be associated with disease. In vitro alpha-Gal activity was reported as 0% of WT (Lukas_2013). 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. |