--- title: "TSC2 E366X (c.1096G>T, rs45517148) | Dante Labs" description: "ClinVar classifies TSC2 E366X as Pathogenic (criteria provided, multiple submitters, no conflicts). Where it sits in the genome, its predicted effect, and the Genome Test reports that look at it." url: "https://dantelabs.com/genes/tsc2/variants/e366x" --- 1. [Genes](https://dantelabs.com/genes) 2. [TSC2](https://dantelabs.com/genes/tsc2) 3. TSC2 E366X Variant # TSC2 E366X NM_000548.5(TSC2):c.1096G>T (p.Glu366Ter) Also known as - p.Glu366Ter - p.E366\* - rs45517148 * ClinVar classification Pathogenic * Review status 2 stars out of 4 criteria provided, multiple submitters, no conflicts * Last evaluated 23 January 2023 Data current to ClinVar release 2026-10-12 · Dante Labs data release 2026.10.19-9814e911 Facts last changed 19 October 2026 ## Summary E366X is a nonsense variant in TSC2: it creates an early stop signal, so the protein the gene encodes is predicted to be cut short. ClinVar classifies it as pathogenic for tuberous sclerosis 2 (criteria provided, multiple submitters, no conflicts). ## ClinVar classifications | Condition | Classification | Review status | Submissions | Last evaluated | | ---------------------------------------------------------------------------------------------------------------------- | -------------- | --------------------------------------------------------------------- | ------------- | --------------- | | tuberous sclerosis 2[ClinVar VCV000012400 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/clinvar/variation/12400/) | Pathogenic | 2 stars out of 4 criteria provided, multiple submitters, no conflicts | 2 submissions | 23 January 2023 | Classifications as ClinVar records them in release 2026-10-12. ClinVar updates them as evidence is reviewed. ## ACMG/AMP criteria The ACMG/AMP criteria E366X meets, from its predicted effect in TSC2, gnomAD and ClinVar. | Criterion | Strength | Points | Rests on | | ------------------------------------------------------- | ----------- | ----------- | ---------------------------------------------------------------------------------------------------------------------------------------- | | PVS1 Null variant where loss of function causes disease | Very strong | +8 | stop_gained on NM_000548.5Expected to cause nonsense-mediated decay Whether loss of function causes disease in this gene was not checked | | PM2 Absent or very rare in population databases | Supporting | +1 | Not seen in gnomAD exomes, gnomAD genomes | | PP5 A reputable source reports it as pathogenic | Supporting | Not counted | ClinVar: Pathogenic (criteria provided, multiple submitters, no conflicts) | On these criteria alone: +9 points, likely pathogenic. Assessed automatically, without functional, computational or family evidence. Not a clinical classification. ## Population frequency How often E366X is seen among the people whose exomes and genomes gnomAD 4.1 brings together. | Dataset | Allele frequency | Allele count | Homozygotes | Commonest in | | -------------- | ---------------- | ------------ | ----------- | ------------ | | gnomAD exomes | Not seen | 0 of 0 | 0 | | | gnomAD genomes | Not seen | 0 of 0 | 0 | | Figures from gnomAD 4.1, as gnomAD publishes them. Groups are genetic ancestry groups as gnomAD infers them. They describe the variant in gnomAD's populations, not anyone's result. [E366X in the gnomAD browser (opens in a new tab)](https://gnomad.broadinstitute.org/variant/16-2060790-G-T?dataset=gnomad_r4) ## Molecular details | Gene | [TSC2](https://dantelabs.com/genes/tsc2) | | --------------------------- | ----------------------------------------------------------------------------------------------------------------------------------------------- | | Transcript | NM_000548.5 MANE Select | | Coding DNA change (HGVS c.) | c.1096G>T | | Protein change (HGVS p.) | p.Glu366Ter p.E366\* | | Predicted consequence | Nonsense (stop gained) [stop_gained (opens in a new tab)](https://purl.obolibrary.org/obo/SO_0001587) | | Predicted impact | High | | Position (GRCh38) | chr16:2060790 G>T | | Position (GRCh37) | chr16:2110791 G>T | | dbSNP ID | [rs45517148 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/snp/rs45517148) | | ClinVar Variation ID | [VCV000012400 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/clinvar/variation/12400/) | | ClinVar Allele ID | 27439 | | ClinGen Allele Registry ID | [CA013758 (opens in a new tab)](https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_canonicalid?canonicalid=CA013758) | | ClinVar name | NM_000548.5(TSC2):c.1096G>T (p.Glu366Ter) | ## TSC2 E366X in other databases - [ClinVar VCV000012400 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/clinvar/variation/12400/) - [dbSNP rs45517148 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/snp/rs45517148) - [ClinGen Allele Registry CA013758 (opens in a new tab)](https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_canonicalid?canonicalid=CA013758) - [gnomAD 16-2060790-G-T (opens in a new tab)](https://gnomad.broadinstitute.org/variant/16-2060790-G-T?dataset=gnomad_r4) - [Ensembl rs45517148 (opens in a new tab)](https://www.ensembl.org/Homo_sapiens/Variation/Explore?v=rs45517148) ## Reports that look at this variant (1) These Genome Test condition reports include E366X among the variants they look at. | Report | Conditions | Inheritance | | ------------------------------------------------------------------------- | ------------------ | ------------------ | | [Tuberous Sclerosis](https://dantelabs.com/conditions/tuberous-sclerosis) | Tuberous Sclerosis | Autosomal dominant | ## Other variants in TSC2 - [A889V Pathogenic/likely pathogenic 2 stars out of 4](https://dantelabs.com/genes/tsc2/variants/a889v) - [c.138+5G>A Pathogenic/likely pathogenic 2 stars out of 4](https://dantelabs.com/genes/tsc2/variants/c-138plus5g-a) - [c.139-1G>A Pathogenic 2 stars out of 4](https://dantelabs.com/genes/tsc2/variants/c-139-1g-a) - [c.139-2A>G Pathogenic 2 stars out of 4](https://dantelabs.com/genes/tsc2/variants/c-139-2a-g) - [c.225+1G>A Pathogenic/likely pathogenic 2 stars out of 4](https://dantelabs.com/genes/tsc2/variants/c-225plus1g-a) - [c.336+1G>T Pathogenic/likely pathogenic 2 stars out of 4](https://dantelabs.com/genes/tsc2/variants/c-336plus1g-t) - [c.336+5G>C Pathogenic/likely pathogenic 2 stars out of 4](https://dantelabs.com/genes/tsc2/variants/c-336plus5g-c) - [c.337-1G>A Pathogenic 2 stars out of 4](https://dantelabs.com/genes/tsc2/variants/c-337-1g-a) - [c.481+1G>A Pathogenic/likely pathogenic 2 stars out of 4](https://dantelabs.com/genes/tsc2/variants/c-481plus1g-a) - [c.599+1G>A Pathogenic 2 stars out of 4](https://dantelabs.com/genes/tsc2/variants/c-599plus1g-a) [All TSC2 variants](https://dantelabs.com/genes/tsc2/variants) ## Limitations This page describes publicly available information about a genetic variant. It is not a diagnosis, and it says nothing about whether you or anyone else carries this variant. Classifications come from ClinVar and change as new evidence is reviewed. A classification here may differ from the one in ClinVar today, or from the one a laboratory reports. Whole genome sequencing with short reads can miss or miscall some variants, particularly in repeated or highly similar stretches of DNA and in large insertions, deletions or rearrangements. If you have questions about a variant in your own results or in your family, talk to a genetic counsellor or your doctor. ## Sources & credits - Classifications from ClinVar (release 2026-10-12), National Center for Biotechnology Information. - Condition terms from the Mondo Disease Ontology (release 2026-10-06), used under CC BY 4.0. - Gene symbols and names from the HUGO Gene Nomenclature Committee (release 2026-10-16). - Allele identifiers from the ClinGen Allele Registry (release 2026-10-19-c4908f54). - Reference SNP identifiers from dbSNP (release b157), National Center for Biotechnology Information. - Gene–disease links from the Gene Curation Coalition, GenCC (release 2026-10-19). - Difficult regions from the Genome in a Bottle Consortium (release v3.6). - Transcripts from MANE (release v1.5), NCBI and EMBL-EBI. - Predicted consequences from mehari (release 0.11.0), with transcript models from cdot. - Built from Dante Labs data release 2026.10.19-9814e911 of 19 October 2026. ## Cite this page APA > Dante Labs. (19 October 2026). TSC2 E366X (c.1096G>T, rs45517148) (Version 2026.10.19-9814e911). Retrieved 21 October 2026, from https\://dantelabs.com/genes/tsc2/variants/e366x Vancouver > Dante Labs. TSC2 E366X (c.1096G>T, rs45517148) \[Internet]. Version 2026.10.19-9814e911. 19 October 2026 \[cited 21 October 2026]. Available from: https\://dantelabs.com/genes/tsc2/variants/e366x Download citation [RIS](https://dantelabs.com/genes/tsc2/variants/e366x/cite.ris) [BibTeX](https://dantelabs.com/genes/tsc2/variants/e366x/cite.bib) [CSL-JSON](https://dantelabs.com/genes/tsc2/variants/e366x/cite.json) ## Read your whole genome From $449 Free shipping · Results in 6–8 weeks [Explore the Genome Test](https://dantelabs.com/whole-genome-sequencing)