--- title: "ACTA1 C376S (c.1127G>C) | Dante Labs" description: "ClinVar classifies ACTA1 C376S as 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/acta1/variants/c376s" --- 1. [Genes](https://dantelabs.com/genes) 2. [ACTA1](https://dantelabs.com/genes/acta1) 3. ACTA1 C376S Variant # ACTA1 C376S NM_001100.4(ACTA1):c.1127G>C (p.Cys376Ser) Also known as - p.Cys376Ser - p.C376S * ClinVar classification Pathogenic * Review status 3 stars out of 4 reviewed by expert panel * Last evaluated 27 August 2024 * Expert panel ClinGen Congenital Myopathies 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 C376S is a missense variant in ACTA1: it changes a single amino acid in the protein the gene encodes. ClinVar classifies it as pathogenic for ACTA1-related myopathy (alpha-actinopathy) (reviewed by expert panel). ## ClinVar classifications | Condition | Classification | Review status | Submissions | Last evaluated | | --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | -------------- | ----------------------------------------- | ------------ | -------------- | | [ACTA1-related myopathy (alpha-actinopathy)](https://dantelabs.com/conditions/congenital-myopathies) [ClinVar VCV003390919 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/clinvar/variation/3390919/) | Pathogenic | 3 stars out of 4 reviewed by expert panel | 1 submission | 27 August 2024 | Classifications as ClinVar records them in release 2026-10-12. ClinVar updates them as evidence is reviewed. ## Where it lies in ACTA1 C376S lies in exon 7 of the 7 in ACTA1's MANE Select transcript, NM_001100.4. [ACTA1 variants in exon 7 →](https://dantelabs.com/genes/acta1/variants?exon=7) [ACTA1's gene diagram →](https://dantelabs.com/genes/acta1#gene-structure) ## Molecular details | Gene | [ACTA1](https://dantelabs.com/genes/acta1) | | --------------------------- | -------------------------------------------------------------------------------------------- | | Transcript | NM_001100.4 MANE Select | | Coding DNA change (HGVS c.) | c.1127G>C | | Protein change (HGVS p.) | p.Cys376Ser p.C376S | | Predicted consequence | Missense [missense_variant (opens in a new tab)](https://purl.obolibrary.org/obo/SO_0001583) | | Predicted impact | Moderate | | Position (GRCh38) | chr1:229431506 C>G | | Position (GRCh37) | chr1:229567253 C>G | | ClinVar Variation ID | [VCV003390919 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/clinvar/variation/3390919/) | | ClinVar Allele ID | 3550005 | | ClinVar name | NM_001100.4(ACTA1):c.1127G>C (p.Cys376Ser) | ## ACTA1 C376S in other databases - [ClinVar VCV003390919 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/clinvar/variation/3390919/) - [gnomAD 1-229431506-C-G (opens in a new tab)](https://gnomad.broadinstitute.org/variant/1-229431506-C-G?dataset=gnomad_r4) - [Ensembl 1-229431506-C-G (opens in a new tab)](https://www.ensembl.org/Homo_sapiens/Location/View?r=1:229431506-229431506) ## Reports that look at this variant (1) These Genome Test condition reports include C376S among the variants they look at. | Report | Conditions | Inheritance | | ------------------------------------------------------------------------------- | ------------------------------------------ | ----------- | | [Congenital Myopathies](https://dantelabs.com/conditions/congenital-myopathies) | ACTA1-related myopathy (alpha-actinopathy) | | ## Other variants in ACTA1 - [c.617-5C>A Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/acta1/variants/c-617-5c-a) - [c.687G>C Pathogenic 3 stars out of 4](https://dantelabs.com/genes/acta1/variants/c-687g-c) - [c.990+1G>T Pathogenic 3 stars out of 4](https://dantelabs.com/genes/acta1/variants/c-990plus1g-t) - [C376F Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/acta1/variants/c376f) - [D13E Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/acta1/variants/d13e) - [D13N Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/acta1/variants/d13n) - [D58N Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/acta1/variants/d58n) - [D181Tfs\*11 Pathogenic 3 stars out of 4](https://dantelabs.com/genes/acta1/variants/d181tfs11) - [D290H Pathogenic 3 stars out of 4](https://dantelabs.com/genes/acta1/variants/d290h) - [E59K Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/acta1/variants/e59k) [All ACTA1 variants](https://dantelabs.com/genes/acta1/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). ACTA1 C376S (c.1127G>C) (Version 2026.10.16-c6eea6bf). Retrieved 16 October 2026, from https\://dantelabs.com/genes/acta1/variants/c376s Vancouver > Dante Labs. ACTA1 C376S (c.1127G>C) \[Internet]. Version 2026.10.16-c6eea6bf. 16 October 2026 \[cited 16 October 2026]. Available from: https\://dantelabs.com/genes/acta1/variants/c376s Download citation [RIS](https://dantelabs.com/genes/acta1/variants/c376s/cite.ris) [BibTeX](https://dantelabs.com/genes/acta1/variants/c376s/cite.bib) [CSL-JSON](https://dantelabs.com/genes/acta1/variants/c376s/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)