--- title: "SCN5A S910L (c.2729C>T, rs199473175) | Dante Labs" description: "ClinVar classifies SCN5A S910L as Pathogenic/likely 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/scn5a/variants/s910l" --- 1. [Genes](https://dantelabs.com/genes) 2. [SCN5A](https://dantelabs.com/genes/scn5a) 3. SCN5A S910L Variant # SCN5A S910L NM_000335.5(SCN5A):c.2729C>T (p.Ser910Leu) Also known as - p.Ser910Leu - p.S910L - rs199473175 * ClinVar classification Pathogenic/likely pathogenic * Review status 2 stars out of 4 criteria provided, multiple submitters, no conflicts * Last evaluated 1 April 2025 Data current to ClinVar release 2026-10-12 · Dante Labs data release 2026.10.19-9814e911 Facts last changed 18 October 2026 ## Summary S910L is a missense variant in SCN5A: it changes a single amino acid in the protein the gene encodes. ClinVar classifies it as pathogenic or likely pathogenic for Brugada syndrome 1 (criteria provided, multiple submitters, no conflicts). ## ClinVar classifications | Condition | Classification | Review status | Submissions | Last evaluated | | -------------------------------------------------------------------------------------------------------------------- | ---------------------------- | --------------------------------------------------------------------- | ------------- | -------------- | | Brugada syndrome 1[ClinVar VCV000067753 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/clinvar/variation/67753/) | Pathogenic/likely pathogenic | 2 stars out of 4 criteria provided, multiple submitters, no conflicts | 2 submissions | 1 April 2025 | Classifications as ClinVar records them in release 2026-10-12. ClinVar updates them as evidence is reviewed. ## ACMG/AMP criteria The ACMG/AMP criteria S910L meets, from its predicted effect in SCN5A, gnomAD and ClinVar. | Criterion | Strength | Rests on | | ----------------------------------------------- | ---------- | -------------------------------------------------------------------------------------------- | | PP5 A reputable source reports it as pathogenic | Supporting | ClinVar: Pathogenic/likely pathogenic (criteria provided, multiple submitters, no conflicts) | On these criteria alone: uncertain significance. Assessed automatically, without functional, computational or family evidence. Not a clinical classification. ## Population frequency How often S910L is seen among the people whose exomes and genomes gnomAD 4.1 brings together. | Dataset | Allele frequency | Allele count | Homozygotes | Commonest in | | -------------- | --------------------- | -------------- | ----------- | -------------------------------- | | gnomAD exomes | 0.00027% 1 in 365,340 | 4 of 1,461,360 | 0 | African/African American: 0.003% | | 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. [S910L in the gnomAD browser (opens in a new tab)](https://gnomad.broadinstitute.org/variant/3-38585749-G-A?dataset=gnomad_r4) ## Where it lies in SCN5A S910L lies in exon 16 of the 28 in SCN5A's MANE Select transcript, NM_000335.5. [SCN5A variants in exon 16 →](https://dantelabs.com/genes/scn5a/variants?exon=16) [SCN5A's gene diagram →](https://dantelabs.com/genes/scn5a#gene-structure) ## Molecular details | Gene | [SCN5A](https://dantelabs.com/genes/scn5a) | | --------------------------- | ----------------------------------------------------------------------------------------------------------------------------------------------- | | Transcript | NM_000335.5 MANE Select | | Coding DNA change (HGVS c.) | c.2729C>T | | Protein change (HGVS p.) | p.Ser910Leu p.S910L | | Predicted consequence | Missense [missense_variant (opens in a new tab)](https://purl.obolibrary.org/obo/SO_0001583) | | Predicted impact | Moderate | | Position (GRCh38) | chr3:38585749 G>A | | Position (GRCh37) | chr3:38627240 G>A | | dbSNP ID | [rs199473175 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/snp/rs199473175) | | ClinVar Variation ID | [VCV000067753 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/clinvar/variation/67753/) | | ClinVar Allele ID | 78648 | | ClinGen Allele Registry ID | [CA016445 (opens in a new tab)](https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_canonicalid?canonicalid=CA016445) | | ClinVar name | NM_000335.5(SCN5A):c.2729C>T (p.Ser910Leu) | ## SCN5A S910L in other databases - [ClinVar VCV000067753 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/clinvar/variation/67753/) - [dbSNP rs199473175 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/snp/rs199473175) - [ClinGen Allele Registry CA016445 (opens in a new tab)](https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_canonicalid?canonicalid=CA016445) - [gnomAD 3-38585749-G-A (opens in a new tab)](https://gnomad.broadinstitute.org/variant/3-38585749-G-A?dataset=gnomad_r4) - [Ensembl rs199473175 (opens in a new tab)](https://www.ensembl.org/Homo_sapiens/Variation/Explore?v=rs199473175) ## Reports that look at this variant (2) These Genome Test condition reports include S910L among the variants they look at. | Report | Conditions | Inheritance | | ----------------------------------------------------------------------------------------------------------------------------------------------- | ------------------------------------- | ------------------ | | [Brugada Syndrome](https://dantelabs.com/conditions/brugada-syndrome) | Brugada Syndrome | | | [Progressive Cardiac Conduction Disease & Sick Sinus Syndrome](https://dantelabs.com/conditions/cardiac-conduction-disease-sick-sinus-syndrome) | SCN5A-Related Cardiac Rhythm Disorder | Autosomal dominant | ## Other variants in SCN5A - [A997S Likely pathogenic 2 stars out of 4](https://dantelabs.com/genes/scn5a/variants/a997s) - [A1427S Likely pathogenic 2 stars out of 4](https://dantelabs.com/genes/scn5a/variants/a1427s) - [c.611+1G>A Pathogenic 2 stars out of 4](https://dantelabs.com/genes/scn5a/variants/c-611plus1g-a) - [c.935-3C>G Likely pathogenic 2 stars out of 4](https://dantelabs.com/genes/scn5a/variants/c-935-3c-g) - [c.1140+1G>A Pathogenic/likely pathogenic 2 stars out of 4](https://dantelabs.com/genes/scn5a/variants/c-1140plus1g-a) - [c.1890G>A Pathogenic/likely pathogenic 2 stars out of 4](https://dantelabs.com/genes/scn5a/variants/c-1890g-a) - [c.4242+1G>C Pathogenic 2 stars out of 4](https://dantelabs.com/genes/scn5a/variants/c-4242plus1g-c) - [c.4434+5G>A Likely pathogenic 2 stars out of 4](https://dantelabs.com/genes/scn5a/variants/c-4434plus5g-a) - [D356N Pathogenic/likely pathogenic 2 stars out of 4](https://dantelabs.com/genes/scn5a/variants/d356n) - [D1274N Pathogenic 2 stars out of 4](https://dantelabs.com/genes/scn5a/variants/d1274n) [All SCN5A variants](https://dantelabs.com/genes/scn5a/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. (18 October 2026). SCN5A S910L (c.2729C>T, rs199473175) (Version 2026.10.19-9814e911). Retrieved 19 October 2026, from https\://dantelabs.com/genes/scn5a/variants/s910l Vancouver > Dante Labs. SCN5A S910L (c.2729C>T, rs199473175) \[Internet]. Version 2026.10.19-9814e911. 18 October 2026 \[cited 19 October 2026]. Available from: https\://dantelabs.com/genes/scn5a/variants/s910l Download citation [RIS](https://dantelabs.com/genes/scn5a/variants/s910l/cite.ris) [BibTeX](https://dantelabs.com/genes/scn5a/variants/s910l/cite.bib) [CSL-JSON](https://dantelabs.com/genes/scn5a/variants/s910l/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)