rs397515870

rs397515870, also known as c.613C>A, p.Pro205Thr and P205T, represents a rare variant in the GLA gene, located on the X chromosome. The minor allele is considered likely to be pathogenic for Fabry disease in ClinVar. Although classically Fabry disease was considered an X-linked recessive disorder, females carrying a single Fabry mutation are often not unaffected carriers since they do develop symptoms requiring medical attention. Evidence provided by one submitter to ClinVar states this: The p.Pro205Thr variant in GLA has been reported in at least 4 individuals with Fabry disease (Blanch 1996, Davis 1996, Schafer 2005, Shimotori 2008), identified by our laboratory in 1 family with HCM (a mother and son) and was absent from large population studies. The p.Pro205Thr variant was associated with decreased alpha-Gal activity in vitro that normalized in the presence of an experimental chaperone (Shimotori 2008, Wu 2011). However, these in vitro assays may not accurately represent biological function. White blood cells from a patient with this variant had increased alpha-Gal activity after the patient was treated with this drug (Wu 2011), and clinical studies are ongoing (Warnock 2015). In summary, this variant is likely to be pathogenic, though additional studies are required to fully establish its clinical significance.

T;T

see discussion at rs397515870

G;T

see discussion at rs397515870