FGF14 (GAA)n [SCA27B] repeat expansion thresholds

[LivBomB]

First of all, I would like to say a big thank you for creating such an amazing website and tool for STRs.

I wanted to bring to your attention the recent study:
https://doi.org/10.1007/s00415-025-13387-4
which reports:

Moreover, (GAA•TTC)200–249 expansions were significantly enriched in patients (8.2%, 11/134) compared to controls (21/822, 2.6%) (OR 3.41, 95% CI 1.56–7.29; Fisher´s exact test, p = 0.0026). However, when the range included (GAA•TTC)180–249 expansions, no significant differences were found between patients (8.9%, 11/134) and controls (5.2%, 43/822) (OR 1.62, 95% CI 0.82–3.20; Fisher´s exact test, p = 0.16).

and

In conclusion, our study of a large cohort of 125 patients with SCA27B provides strong evidence that (GAA•TTC)200–249 alleles can be pathogenic in some individuals.

A few other studies also mention the 200-249 range.
Currently, your website and JSON file define FGF14 repeat ranges as:

• ≤179 Benign / 180–319 Intermediate / ≥320 Pathogenic

Given the evidence in the paper mentioned above, it might be more appropriate to consider one of the following alternative groupings:

• ≤199 Benign / 200–299 Intermediate / ≥300 Pathogenic
• ≤199 Benign / 200–249 Intermediate / ≥250 Pathogenic

Or until additional data are available for the 200-249 range:

• ≤249 Benign / 250–299 Intermediate / ≥300 Pathogenic

The ≥300 repeats have been well established as fully pathogenic and 250–299 as reduced penetrance since the identification of the FGF14 (GAA)n repeat expansion. It may be worth adjusting the thresholds to better reflect the current evidence.

[Macayla-weiner]

Hello, Thank you for sharing this! While those probably are the average thresholds, our goal with reporting them is to capture the entire range reported across studies. So, since Mohren et al. reported both lower thresholds and the longest repeat we've seen, we use those.

[LivBomB]

That is perfectly understandable.
Thanks for the reply.