| Geno
|
Mag
|
Summary
|
| (A;C)
|
3.8
|
Likely miscall in both 23andMe and Ancestry data; otherwise, possible frontotemporal dementia mutation
|
| (C;C)
|
0
|
common in clinvar
|
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.
[PMID 23596077
] 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.
] 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.
