Rs1064651

rs1064651, also known as Asp448His or D448H, is a SNP in exon 9 of the GBA gene on chromosome 1. As the protein was originally numbered, though, this variation occurred at amino acid 409 (rather than 448), so the scientific literature still often refers to this mutation as Asp409His or D409H.

Mutations in both copies of a person's GBA gene may lead to Gaucher's disease, an autosomal recessive disorder. When one of the mutations is the D409H mutation, the clinical description may be Gaucher disease type 3C, involving valvular heart disease. However, the clinical presentation appears to be highly variable as well as dependent on which two mutations are present. For more information, see OMIM 606463.0006.

Be aware that since this mutation is due to a G>C (tranversion) when oriented in the direction the gene is transcribed, interpretation can be problematic due to orientation issues involving ambiguous flips. To make matters even more confusing, in the past, dbSNP (erroneously) defined the minus strand 'ancestral' (i.e. normal) allele as C, although it currently (correctly) defines the minus strand ancestral allele as G. In SNPedia, the orientation is set to the plus strand, which means the normal allele (for the plus strand) is C. This is also the orientation currently used by 23andMe.