rs63751243

rs63751243, also known as c.26C>A, p.Ala9Asp and A9D, represents a relatively rare mutation in the GRN gene on chromosome 17. OMIM reports the rs63751243(A) allele as representing a dominantly inherited mutation associated with ubiquitin-positive frontotemporal lobar degeneration. ClinVar cites OMIM but lacks an actual statement as to pathogenicity for unknown reasons. Among Promethease users, the rare allele (i.e. the heterozygous genotype) is seen in a bit under 1 in 1000 people, primarily in reports from genotyped 23andMe and Ancestry customers. In the ExAc sequencing database, the C>T change was seen in less than 1 in 60,000 people, and the C>A change was seen zero times. The significantly higher (>60x) rate of calls for this mutation in 23andMe customers indicates it is a mutation prone to be miscalled for customers of both Ancestry and 23andMe, and any putatively positive results for this clinically significant mutation should be questioned and tested with a clinically valid test. Three rs63751243(A;C) behavioral variant frontotemporal dementia patients were evaluated clinically and were found to exhibit aphasia, extrapyramidal features, and, notably, amyotrophic lateral sclerosis.

A;C

See discussion at rs63751243; if you are not a customer of either 23andMe or Ancestry, and your Promethease report shows this genotype, please email us (info@promethease.com), letting us know what company produced your data and when they processed your DNA sample.