Add ATTCC motif to ATXN10

[juniper-lake]

Presence and count of the ATTCC motif potentially affects pathogenicity/penetrance/symptoms in SCA10. I am currently looking at a parent/proband that has an expansion of both ATTCT and ATTCC.

Published evidence:

• ATTCT and ATTCC repeat expansions in the ATXN10 gene affect disease penetrance of spinocerebellar ataxia type 10 "Our findings suggest that the pure (ATTCT)n expansion is non-pathogenic, while repeat interruptions, e.g., (ATTCC)n, are necessary to cause SCA10."
• Parkinson’s disease associated with pure ATXN10 repeat expansion "Thus, the ATTCC interruption is likely a novel genetic modifier for the clinical occurrence of seizures in SCA10."

[Macayla-weiner]

Hello! Thank you for this suggestion. We plan to add an "interruptions" segment in that "alleles" section, so this will be added in that update (which may take some time).

[juniper-lake]

Sounds great, but what distinguishes an “interruption” from “motif”? If it’s a motif, then tools like TRGT provide motif counts for it.

[hdashnow]

In my mind, a motif is repeated in tandem, and an interruption typically occurs once or a small number of times, typically interspersed.

For TRGT, the distinction is probably arbitrary, as it's just a matter of annotation/visualization, and interruptions could be included as alternate motifs. For the interpretation of pathogenicity, separating the two would likely be more useful.

In your work, what do you think would be most useful?