> For the complete documentation index, see [llms.txt](https://help.connected.illumina.com/llms.txt). Markdown versions of documentation pages are available by appending `.md` to page URLs; this page is available as [Markdown](https://help.connected.illumina.com/emedgene/emedgene-analyze-manual/tertiary-analysis-pipeline/str_calling_and_interpretation.md).

# Tertiary analysis of STR variants

**Short tandem repeats (STRs)** are genomic regions composed of repeated short DNA sequences. When STRs expand beyond the normal range, they can cause mutations known as **repeat expansions**, which may alter gene expression or function.

Expansion of these sequences in certain genes is the underlying mechanism for a group of inherited conditions called **repeat expansion disorders**. These disorders primarily affect the nervous and muscular systems, leading to diseases such as Fragile X syndrome, amyotrophic lateral sclerosis and Huntington’s disease.

The platform shows repeat counts per allele and highlights values that fall in **normal**, **intermediate** or **pathogenic** ranges (where known).

## STR loci filtering and prioritization

STR variants outside the genomic regions specified in the DRAGEN v4.2 `expanded` variant catalog are **excluded before tertiary analysis**. This applies regardless of whether DRAGEN (internal or external) or another pipeline was used for the secondary analysis and irrespective of the DRAGEN version.

{% file src="/files/lrw1ojHlbWkuXUGmUlKt" %}

{% file src="/files/Aq4LMvsMmyYQoQ9vRFfS" %}

Variant calling reliability and availability of meaningful annotations for STR loci can vary. To reduce noise and ensure high-confidence calls, **only a curated subset of STR loci is included in AI Shortlist analysis** (Table 1). STR loci were curated by Emedgene based on strict criteria to ensure technical accuracy:

* **Validated genotype–phenotype associations and established pathogenicity**. Loci must have well-documented links to disease and specific phenotypes. This avoids reporting variants with unclear implications.
* **Reliable calling performance**. STR calling is technically challenging. Some loci are prone to false positives or inaccurate sizing. The subset includes loci that DRAGEN-STR can call consistently and accurately. This avoids reporting low-quality variants.
* **Expansion thresholds**. Loci with defined pathogenic thresholds (e.g., number of repeats linked to disease) are prioritized. This avoids reporting variants that lack clear interpretation guidelines.

**STRs that are not tagged by AI Shortlist are still included in the analysis**. This means they will not be automatically prioritized or tagged as Most Likely or Candidate by the AI. However, these loci remain available for manual review and tagging.

**Table 1. STR loci considered by AI Shortlist**

<table data-header-hidden="false" data-header-sticky data-full-width="true"><thead><tr><th width="43" data-type="number">№</th><th width="126">STR locus</th><th width="145">Genomic region (hg38)</th><th>Associated condition(s)</th><th width="122">Inheritance mode</th><th width="100">Repeat unit</th></tr></thead><tbody><tr><td>1</td><td><strong>AR</strong></td><td>X:67545316-67545385</td><td>Spinal and bulbar muscular atrophy (SBMA)</td><td>XR</td><td>GCA</td></tr><tr><td>2</td><td><strong>ATN1</strong></td><td>12:6936716-6936773</td><td>Dentatorubral-pallidoluysian atrophy (DRPLA)</td><td>AD</td><td>CAG</td></tr><tr><td>3</td><td><strong>ATN1</strong></td><td>12:6923960-6923977</td><td></td><td></td><td>TG</td></tr><tr><td>4</td><td><strong>ATN1</strong></td><td>12:6925117-6925140</td><td></td><td></td><td>GT</td></tr><tr><td>5</td><td><strong>ATN1</strong></td><td>12:6930800-6930827</td><td></td><td></td><td>AATA</td></tr><tr><td>6</td><td><strong>ATXN1</strong></td><td>6:16327633-16327723</td><td>Spinocerebellar ataxia 1 (SCA1)</td><td>AD</td><td>TGC</td></tr><tr><td>7</td><td><strong>ATXN10</strong></td><td>22:45795354-45795424</td><td>Spinocerebellar ataxia 10 (SCA10)</td><td>AD</td><td>ATTCT</td></tr><tr><td>8</td><td><strong>ATXN2</strong></td><td>12:111598949-111599018</td><td>Spinocerebellar ataxia 2 (SCA2)</td><td>AD</td><td>GCT</td></tr><tr><td>9</td><td><strong>ATXN2</strong></td><td>12:111461472-111461481</td><td></td><td></td><td>AAAAT</td></tr><tr><td>10</td><td><strong>ATXN2</strong></td><td>12:111464247-111464282</td><td></td><td></td><td>GT</td></tr><tr><td>11</td><td><strong>ATXN2</strong></td><td>12:111483194-111483237</td><td></td><td></td><td>AC</td></tr><tr><td>12</td><td><strong>ATXN2</strong></td><td>12:111487453-111487472</td><td></td><td></td><td>TTTA</td></tr><tr><td>13</td><td><strong>ATXN2</strong></td><td>12:111568991-111569015</td><td></td><td></td><td>TTTTG</td></tr><tr><td>14</td><td><strong>ATXN2</strong></td><td>12:111577256-111577279</td><td></td><td></td><td>TTAT</td></tr><tr><td>15</td><td><strong>ATXN2</strong></td><td>12:111588188-111588219</td><td></td><td></td><td>AAAT</td></tr><tr><td>16</td><td><strong>ATXN2</strong></td><td>12:111591364-111591375</td><td></td><td></td><td>TAAAAA</td></tr><tr><td>17</td><td><strong>ATXN2</strong></td><td>12:111591756-111591773</td><td></td><td></td><td>TTG</td></tr><tr><td>18</td><td><strong>ATXN2</strong></td><td>12:111596205-111596244</td><td></td><td></td><td>AC</td></tr><tr><td>19</td><td><strong>ATXN2</strong></td><td>12:111596373-111596388</td><td></td><td></td><td>CA</td></tr><tr><td>20</td><td><strong>ATXN2</strong></td><td>12:111600935-111600958</td><td></td><td></td><td>AAAT</td></tr><tr><td>21</td><td><strong>ATXN2</strong></td><td>12:111604087-111604106</td><td></td><td></td><td>AT</td></tr><tr><td>22</td><td><strong>ATXN3</strong></td><td>14:92071009-92071041</td><td>Spinocerebellar ataxia 3 (SCA3)</td><td>AD</td><td>GCT</td></tr><tr><td>23</td><td><strong>ATXN3</strong></td><td>14:92059829-92059848</td><td></td><td></td><td>AAAG</td></tr><tr><td>24</td><td><strong>ATXN3</strong></td><td>14:92065889-92065900</td><td></td><td></td><td>AAT</td></tr><tr><td>25</td><td><strong>ATXN3</strong></td><td>14:92078361-92078376</td><td></td><td></td><td>TTAT</td></tr><tr><td>26</td><td><strong>ATXN7</strong></td><td>3:63912684-63912714</td><td>Spinocerebellar ataxia 7 (SCA7)</td><td>AD</td><td>GCA</td></tr><tr><td>27</td><td><strong>ATXN7</strong></td><td>3:63912714-63912725</td><td></td><td></td><td>GCC</td></tr><tr><td>28</td><td><strong>ATXN8OS</strong></td><td>13:70139383-70139428</td><td></td><td></td><td>CTG</td></tr><tr><td>29</td><td><strong>ATXN8OS</strong></td><td>13:70139353-70139382</td><td>Spinocerebellar ataxia 8 (SCA8)</td><td>AD</td><td>CTA</td></tr><tr><td>30</td><td><strong>ATXN8OS</strong></td><td>13:70115027-70115046</td><td></td><td></td><td>GT</td></tr><tr><td>31</td><td><strong>ATXN8OS</strong></td><td>13:70126607-70126620</td><td></td><td></td><td>TA</td></tr><tr><td>32</td><td><strong>ATXN8OS</strong></td><td>13:70129375-70129402</td><td></td><td></td><td>TG</td></tr><tr><td>33</td><td><strong>C9ORF72</strong></td><td>9:27573528-27573546</td><td>Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 (FTDALS1)</td><td>AD</td><td>GGCCCC</td></tr><tr><td>34</td><td><strong>CACNA1A</strong></td><td>19:13207858-13207897</td><td>Spinocerebellar ataxia 6 (SCA6)</td><td>AD</td><td>CTG</td></tr><tr><td>35</td><td><strong>CNBP</strong></td><td>3:129172576-129172656</td><td></td><td></td><td>CAGA</td></tr><tr><td>36</td><td><strong>DMPK</strong></td><td>19:45770204-45770264</td><td>Myotonic dystrophy 1 (DM1)</td><td>AD</td><td>CAG</td></tr><tr><td>37</td><td><strong>FMR1</strong></td><td>X:147912050-147912110</td><td>Fragile X syndrome (FXS)</td><td>XD</td><td>CGG</td></tr><tr><td>38</td><td><strong>FXN</strong></td><td>9:69037286-69037304</td><td></td><td></td><td>GAA</td></tr><tr><td>39</td><td><strong>FXN</strong></td><td>9:69037261-69037285</td><td>Friedreich ataxia (FRDA)</td><td>AR</td><td>A</td></tr><tr><td>40</td><td><strong>HTT</strong></td><td>4:3074876-3074933</td><td>Huntington disease (HD)</td><td>AD</td><td>CAG</td></tr><tr><td>41</td><td><strong>HTT</strong></td><td>4:3074939-3074965</td><td></td><td></td><td>CCG</td></tr><tr><td>42</td><td><strong>JPH3</strong></td><td>16:87604287-87604329</td><td>Huntington disease-like 2 (HDL2)</td><td>AD</td><td>CTG</td></tr><tr><td>43</td><td><strong>NOP56</strong></td><td>20:2652733-2652757</td><td>Spinocerebellar ataxia 36 (SCA36)</td><td>AD</td><td>GGCCTG</td></tr><tr><td>44</td><td><strong>NOP56</strong></td><td>20:2652757-2652774</td><td></td><td></td><td>CGCCTG</td></tr><tr><td>45</td><td><strong>PPP2R2B</strong></td><td>5:146878727-146878757</td><td>Spinocerebellar ataxia 12 (SCA12)</td><td>AD</td><td>GCT</td></tr><tr><td>46</td><td><strong>TBP</strong></td><td>6:170561906-170562017</td><td>Spinocerebellar ataxia 17 (SCA17)</td><td>AD</td><td>GCA</td></tr></tbody></table>


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