Variant
RET C618S
NM_020975.6(RET):c.1853G>C (p.Cys618Ser)
- p.C618S:TGC>TCC
- p.Cys618Ser
- p.C618S
- rs79781594
- ClinVar classification
- Pathogenic
- Review status
- 2 stars out of 4criteria provided, multiple submitters, no conflicts
- Last evaluated
- 2 December 2025
Data current to ClinVar release 2026-10-12 · Dante Labs data release 2026.10.19-9814e911Facts last changed 18 October 2026
This page as data
Add .json to the page's address, or ask for application/json, to read it as JSON.
library(jsonlite)
url <- "https://dantelabs.com/genes/ret/variants/c618s.json"
page <- fromJSON(url)
page$variant$nameSummary
C618S is a missense variant in RET: it changes a single amino acid in the protein the gene encodes. ClinVar classifies it as pathogenic for Multiple Endocrine Neoplasia Type 2 (criteria provided, multiple submitters, no conflicts).
ClinVar classifications
| Condition | Classification | Review status | Submissions | Last evaluated |
|---|---|---|---|---|
| Multiple Endocrine Neoplasia Type 2ClinVar VCV000013914 (opens in a new tab) | Pathogenic | 2 stars out of 4criteria provided, multiple submitters, no conflicts | 3 submissions | 2 December 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 C618S meets, from its predicted effect in RET, gnomAD and ClinVar.
| Criterion | Strength | Rests on |
|---|---|---|
| PM2Absent or very rare in population databases | Supporting | Not seen in gnomAD exomes, gnomAD genomes |
| PP5A reputable source reports it as pathogenic | Supporting | ClinVar: 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 C618S 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.
Where it lies in RET
C618S lies in exon 10 of the 20 in RET's MANE Select transcript, NM_020975.6.
Molecular details
| Gene | RET |
|---|---|
| Transcript | NM_020975.6MANE Select |
| Coding DNA change (HGVS c.) | c.1853G>C |
| Protein change (HGVS p.) | p.Cys618Serp.C618S |
| Predicted consequence | Missensemissense_variant (opens in a new tab) |
| Predicted impact | Moderate |
| Position (GRCh38) | chr10:43113649 G>C |
| Position (GRCh37) | chr10:43609097 G>C |
| dbSNP ID | rs79781594 (opens in a new tab) |
| ClinVar Variation ID | VCV000013914 (opens in a new tab) |
| ClinVar Allele ID | 28953 |
| ClinGen Allele Registry ID | CA008013 (opens in a new tab) |
| ClinVar name | NM_020975.6(RET):c.1853G>C (p.Cys618Ser) |
| Other names | p.C618S:TGC>TCC |
RET C618S in other databases
Reports that look at this variant (2)
These Genome Test condition reports include C618S among the variants they look at.
| Report | Conditions | Inheritance |
|---|---|---|
| Malignant Endocrine Neoplasm | Malignant Endocrine Neoplasm | |
| Multiple Endocrine Neoplasia | Autosomal dominant | |
| Thyroid Cancer | Thyroid Tumor | |
| Thyroid Cancer | ||
| Thyroid Gland Carcinoma | ||
| Multiple Endocrine Neoplasia Type 2 | Autosomal dominant | |
| Thyroid Gland Disorder |
Other variants in RET
- c.1852T>APathogenic2 stars out of 4
- c.1858T>APathogenic/likely pathogenic2 stars out of 4
- c.1947G>APathogenic/likely pathogenic2 stars out of 4
- c.1998G>CPathogenic/likely pathogenic2 stars out of 4
- c.2370G>TPathogenic2 stars out of 4
- c.2410G>CPathogenic/likely pathogenic2 stars out of 4
- C609RPathogenic2 stars out of 4
- C609YPathogenic2 stars out of 4
- C611FPathogenic2 stars out of 4
- C611YPathogenic2 stars out of 4
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
Dante Labs. (18 October 2026). RET C618S (c.1853G>C, rs79781594) (Version 2026.10.19-9814e911). Retrieved 20 October 2026, from https://dantelabs.com/genes/ret/variants/c618s
Dante Labs. RET C618S (c.1853G>C, rs79781594) [Internet]. Version 2026.10.19-9814e911. 18 October 2026 [cited 20 October 2026]. Available from: https://dantelabs.com/genes/ret/variants/c618s
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