--- title: "LDLR C681W (c.2043C>G, rs121908031) | Dante Labs" description: "ClinVar classifies LDLR C681W 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/ldlr/variants/c681w" --- 1. [Genes](https://dantelabs.com/genes) 2. [LDLR](https://dantelabs.com/genes/ldlr) 3. LDLR C681W Variant # LDLR C681W NM_000527.5(LDLR):c.2043C>G (p.Cys681Trp) Also known as - p.Cys681Trp - p.C681W - rs121908031 * ClinVar classification Pathogenic * Review status 3 stars out of 4 reviewed by expert panel * Last evaluated 18 June 2021 * Expert panel ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel Data current to ClinVar release 2026-10-12 · Dante Labs data release 2026.10.16-c6eea6bf Facts last changed 16 October 2026 ## Summary C681W is a missense variant in LDLR: it changes a single amino acid in the protein the gene encodes. ClinVar classifies it as pathogenic for hypercholesterolemia, familial, 1 (reviewed by expert panel). ## ClinVar classifications | Condition | Classification | Review status | Submissions | Last evaluated | | ------------------------------------------------------------------------------------------------------------------------------------ | -------------- | ----------------------------------------- | ------------ | -------------- | | hypercholesterolemia, familial, 1[ClinVar VCV000252188 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/clinvar/variation/252188/) | Pathogenic | 3 stars out of 4 reviewed by expert panel | 1 submission | 18 June 2021 | Classifications as ClinVar records them in release 2026-10-12. ClinVar updates them as evidence is reviewed. ## Where it lies in LDLR C681W lies in exon 14 of the 18 in LDLR's MANE Select transcript, NM_000527.5. [LDLR variants in exon 14 →](https://dantelabs.com/genes/ldlr/variants?exon=14) [LDLR's gene diagram →](https://dantelabs.com/genes/ldlr#gene-structure) ## Molecular details | Gene | [LDLR](https://dantelabs.com/genes/ldlr) | | --------------------------- | --------------------------------------------------------------------------------------------------------------------------------------------------- | | Transcript | NM_000527.5 MANE Select | | Coding DNA change (HGVS c.) | c.2043C>G | | Protein change (HGVS p.) | p.Cys681Trp p.C681W | | Predicted consequence | Missense [missense_variant (opens in a new tab)](https://purl.obolibrary.org/obo/SO_0001583) | | Predicted impact | Moderate | | Position (GRCh38) | chr19:11120425 C>G | | Position (GRCh37) | chr19:11231101 C>G | | dbSNP ID | [rs121908031 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/snp/rs121908031) | | ClinVar Variation ID | [VCV000252188 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/clinvar/variation/252188/) | | ClinVar Allele ID | 246483 | | ClinGen Allele Registry ID | [CA10585743 (opens in a new tab)](https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_canonicalid?canonicalid=CA10585743) | | ClinVar name | NM_000527.5(LDLR):c.2043C>G (p.Cys681Trp) | ## LDLR C681W in other databases - [ClinVar VCV000252188 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/clinvar/variation/252188/) - [dbSNP rs121908031 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/snp/rs121908031) - [ClinGen Allele Registry CA10585743 (opens in a new tab)](https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_canonicalid?canonicalid=CA10585743) - [gnomAD 19-11120425-C-G (opens in a new tab)](https://gnomad.broadinstitute.org/variant/19-11120425-C-G?dataset=gnomad_r4) - [Ensembl rs121908031 (opens in a new tab)](https://www.ensembl.org/Homo_sapiens/Variation/Explore?v=rs121908031) ## Reports that look at this variant (2) These Genome Test condition reports include C681W among the variants they look at. | Report | Conditions | Inheritance | | ----------------------------------------------------------------------------------------------- | ----------------------------- | ----------- | | [Familial Hypercholesterolemia](https://dantelabs.com/conditions/familial-hypercholesterolemia) | familial hypercholesterolemia | | | [Hyperlipidemia](https://dantelabs.com/conditions/hyperlipidemia) | Hyperlipidemia | | ## Other variants in LDLR - [A399D Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/ldlr/variants/a399d) - [A399T Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/ldlr/variants/a399t) - [A431P Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/ldlr/variants/a431p) - [A431T Pathogenic 3 stars out of 4](https://dantelabs.com/genes/ldlr/variants/a431t) - [A540S Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/ldlr/variants/a540s) - [A540T Pathogenic 3 stars out of 4](https://dantelabs.com/genes/ldlr/variants/a540t) - [A612Rfs\*50 Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/ldlr/variants/a612rfs50) - [A697P Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/ldlr/variants/a697p) - [c.1A>C Pathogenic 3 stars out of 4](https://dantelabs.com/genes/ldlr/variants/c-1a-c) - [c.1A>G Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/ldlr/variants/c-1a-g) [All LDLR variants](https://dantelabs.com/genes/ldlr/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). LDLR C681W (c.2043C>G, rs121908031) (Version 2026.10.16-c6eea6bf). Retrieved 16 October 2026, from https\://dantelabs.com/genes/ldlr/variants/c681w Vancouver > Dante Labs. LDLR C681W (c.2043C>G, rs121908031) \[Internet]. Version 2026.10.16-c6eea6bf. 16 October 2026 \[cited 16 October 2026]. Available from: https\://dantelabs.com/genes/ldlr/variants/c681w Download citation [RIS](https://dantelabs.com/genes/ldlr/variants/c681w/cite.ris) [BibTeX](https://dantelabs.com/genes/ldlr/variants/c681w/cite.bib) [CSL-JSON](https://dantelabs.com/genes/ldlr/variants/c681w/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)