--- title: "RYR1 D2129E (c.6387C>G, rs117886618) | Dante Labs" description: "ClinVar classifies RYR1 D2129E as Likely pathogenic (reviewed by expert panel). Where it sits in the genome, its predicted effect, and the Genome Test reports that look at it." url: "https://dantelabs.com/genes/ryr1/variants/d2129e" --- 1. [Genes](https://dantelabs.com/genes) 2. [RYR1](https://dantelabs.com/genes/ryr1) 3. RYR1 D2129E Variant # RYR1 D2129E NM_000540.3(RYR1):c.6387C>G (p.Asp2129Glu) Also known as - p.Asp2129Glu - p.D2129E - rs117886618 * ClinVar classification Likely pathogenic * Review status 3 stars out of 4 reviewed by expert panel * Last evaluated 1 August 2025 * Expert panel ClinGen Malignant Hyperthermia Susceptibility Variant Curation Expert Panel, ClinGen Data current to ClinVar release 2026-10-12 · Dante Labs data release 2026.10.16-c6eea6bf Facts last changed 16 October 2026 ## Summary D2129E is a missense variant in RYR1: it changes a single amino acid in the protein the gene encodes. ClinVar classifies it as likely pathogenic for malignant hyperthermia, susceptibility to, 1 (reviewed by expert panel). ## ClinVar classifications | Condition | Classification | Review status | Submissions | Last evaluated | | ----------------------------------------------------------------------------------------------------------------------------------------------- | ----------------- | ----------------------------------------- | ------------ | -------------- | | malignant hyperthermia, susceptibility to, 1[ClinVar VCV000133157 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/clinvar/variation/133157/) | Likely pathogenic | 3 stars out of 4 reviewed by expert panel | 1 submission | 1 August 2025 | Classifications as ClinVar records them in release 2026-10-12. ClinVar updates them as evidence is reviewed. ## Where it lies in RYR1 D2129E lies in exon 39 of the 106 in RYR1's MANE Select transcript, NM_000540.3. [RYR1 variants in exon 39 →](https://dantelabs.com/genes/ryr1/variants?exon=39) [RYR1's gene diagram →](https://dantelabs.com/genes/ryr1#gene-structure) ## Molecular details | Gene | [RYR1](https://dantelabs.com/genes/ryr1) | | --------------------------- | ----------------------------------------------------------------------------------------------------------------------------------------------- | | Transcript | NM_000540.3 MANE Select | | Coding DNA change (HGVS c.) | c.6387C>G | | Protein change (HGVS p.) | p.Asp2129Glu p.D2129E | | Predicted consequence | Missense [missense_variant (opens in a new tab)](https://purl.obolibrary.org/obo/SO_0001583) | | Predicted impact | Moderate | | Position (GRCh38) | chr19:38494464 C>G | | Position (GRCh37) | chr19:38985104 C>G | | dbSNP ID | [rs117886618 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/snp/rs117886618) | | ClinVar Variation ID | [VCV000133157 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/clinvar/variation/133157/) | | ClinVar Allele ID | 136904 | | ClinGen Allele Registry ID | [CA024575 (opens in a new tab)](https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_canonicalid?canonicalid=CA024575) | | ClinVar name | NM_000540.3(RYR1):c.6387C>G (p.Asp2129Glu) | ## RYR1 D2129E in other databases - [ClinVar VCV000133157 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/clinvar/variation/133157/) - [dbSNP rs117886618 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/snp/rs117886618) - [ClinGen Allele Registry CA024575 (opens in a new tab)](https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_canonicalid?canonicalid=CA024575) - [gnomAD 19-38494464-C-G (opens in a new tab)](https://gnomad.broadinstitute.org/variant/19-38494464-C-G?dataset=gnomad_r4) - [Ensembl rs117886618 (opens in a new tab)](https://www.ensembl.org/Homo_sapiens/Variation/Explore?v=rs117886618) ## Reports that look at this variant (1) These Genome Test condition reports include D2129E among the variants they look at. | Report | Conditions | Inheritance | | --------------------------------------------------------------------------------------------------------------- | ------------------------------------- | ------------------ | | [Malignant Hyperthermia Susceptibility](https://dantelabs.com/conditions/malignant-hyperthermia-susceptibility) | Malignant Hyperthermia Susceptibility | Autosomal dominant | ## Other variants in RYR1 - [A152D Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/ryr1/variants/a152d) - [A2200V Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/ryr1/variants/a2200v) - [A2350T Pathogenic 3 stars out of 4](https://dantelabs.com/genes/ryr1/variants/a2350t) - [A2428T Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/ryr1/variants/a2428t) - [A2437V Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/ryr1/variants/a2437v) - [A4338Gfs\*238 Pathogenic 3 stars out of 4](https://dantelabs.com/genes/ryr1/variants/a4338gfs238) - [c.742G>C Pathogenic 3 stars out of 4](https://dantelabs.com/genes/ryr1/variants/c-742g-c) - [c.958-2_958del Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/ryr1/variants/c-958-2to958del) - [c.1021G>C Pathogenic 3 stars out of 4](https://dantelabs.com/genes/ryr1/variants/c-1021g-c) - [c.1925+1G>C Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/ryr1/variants/c-1925plus1g-c) [All RYR1 variants](https://dantelabs.com/genes/ryr1/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 2026-10-16-c4908f54). - Reference SNP identifiers from dbSNP (release b157), National Center for Biotechnology Information. - Gene–disease links from the Gene Curation Coalition, GenCC (release 2026-10-16). - 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 2026.10.16-c6eea6bf of 16 October 2026. ## Cite this page APA > Dante Labs. (16 October 2026). RYR1 D2129E (c.6387C>G, rs117886618) (Version 2026.10.16-c6eea6bf). Retrieved 16 October 2026, from https\://dantelabs.com/genes/ryr1/variants/d2129e Vancouver > Dante Labs. RYR1 D2129E (c.6387C>G, rs117886618) \[Internet]. Version 2026.10.16-c6eea6bf. 16 October 2026 \[cited 16 October 2026]. Available from: https\://dantelabs.com/genes/ryr1/variants/d2129e Download citation [RIS](https://dantelabs.com/genes/ryr1/variants/d2129e/cite.ris) [BibTeX](https://dantelabs.com/genes/ryr1/variants/d2129e/cite.bib) [CSL-JSON](https://dantelabs.com/genes/ryr1/variants/d2129e/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)