VCV001301626.6 - ClinVar

NM_001807.6(CEL):c.337C>T (p.Gln113Ter)

Germline

Classification

criteria provided, conflicting classifications. Learn more about how ClinVar calculates review status.

Conflicting classifications of pathogenicity
Pathogenic (1); Likely pathogenic (1); Uncertain significance (2); Likely benign (1)

5 out of 5 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001807.6(CEL):c.337C>T (p.Gln113Ter)

Variation ID: 1301626 Accession: VCV001301626.6

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 9q34.13 9: 133064759 (GRCh38) [ NCBI UCSC ] 9: 135940146 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Oct 30, 2021	Jul 14, 2026	Jun 17, 2026

HGVS

Nucleotide	Protein	Molecular consequence
NM_001807.6:c.337C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001798.3:p.Gln113Ter	nonsense
NC_000009.12:g.133064759C>T
NC_000009.11:g.135940146C>T
NG_016394.1:g.7782C>T

Protein change

Q113*

Other names

Canonical SPDI

NC_000009.12:133064758:C:T

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Trans-Omics for Precision Medicine (TOPMed) 0.00001

Links

ClinGen: CA375391400 dbSNP: rs1200339761 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
CEL		-	-	GRCh38 GRCh37	428	481

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Maturity-onset diabetes of the young type 8	Conflicting classifications of pathogenicity (4)	criteria provided, conflicting classifications	Jun 17, 2026	RCV001733579.16
Maturity-onset diabetes of the young	Pathogenic (1)	criteria provided, single submitter	Oct 4, 2024	RCV004798919.2

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Likely pathogenic (Aug 24, 2022) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Maturity-onset diabetes of the young type 8	HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology Study: HudsonAlpha-AGHI-WGS Accession: SCV002762751.1 First in ClinVar: Dec 17, 2022 Last updated: Dec 17, 2022	Comment: show ACMG codes:PVS1_VeryStrong, PM2_Moderate (less) Observation: 1 Collection method: research Allele origin: paternal Affected status: yes more Observation 1 Collection method: research Allele origin: paternal Affected status: yes Number of individuals with the variant: 1 Clinical Features: Global developmental delay (present) , Delayed speech and language development (present) , Autistic behavior (present) , Diabetes mellitus type 1 (present) , Celiac disease (present)

Uncertain significance (Mar 18, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Maturity-onset diabetes of the young type 8 (Autosomal dominant inheritance)	Intergen Genetics and Rare Diseases Diagnosis Center Accession: SCV004801332.1 First in ClinVar: Mar 23, 2024 Last updated: Mar 23, 2024	Comment: show The assertion regarding the gene and its association with the disease is currently uncertain. It remains unknown whether loss-of-function variants of the gene contribute to the phenotype. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: no more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: no Zygosity: 1 Single Heterozygote

Uncertain significance (Mar 25, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Maturity-onset diabetes of the young type 8	Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre Accession: SCV004806343.1 First in ClinVar: Apr 06, 2024 Last updated: Apr 06, 2024	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Oct 04, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Maturity-onset diabetes of the young	Dubai Health Genomic Medicine Center, Dubai Health Accession: SCV002818192.2 First in ClinVar: Jan 07, 2023 Last updated: Dec 07, 2024	Comment: show PVS1,PM2 (less) Observation: 1 Collection method: research Allele origin: germline Affected status: yes Observation 1 Collection method: research Allele origin: germline Affected status: yes

Likely benign (Jun 17, 2026) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Maturity-onset diabetes of the young type 8 (Autosomal dominant inheritance)	Dubai Health Genomic Medicine Center, Dubai Health Accession: SCV001984213.2 First in ClinVar: Oct 30, 2021 Last updated: Jul 14, 2026 Comment: The p.Gln116* variant in CEL has not been previously reported in individuals with disease and but was identified in 2/1984 (0.1% 0 homozygotes) total alleles … (more) The p.Gln116* variant in CEL has not been previously reported in individuals with disease and but was identified in 2/1984 (0.1% 0 homozygotes) total alleles in the Greater Middle East (GME) variome Database. This nonsense variant leads to a premature termination codon at position 116 which is predicted to lead to a truncated or absent protein. In summary this variant meets our criteria to be classified as pathogenicity. (less)	Comment: show NM_001807.6(CEL):c.337C>T; p.(Gln113)- Heterozygous likely benign The p.Gln116 variant in CEL has not been previously reported in individuals with maturity-onset diabetes of the young (MODY). In our internal cohort, this variant was identified in 85 individuals (2 homozygotes), of which 1% were diabetic, 20% pre-diabetic, and 79% healthy (including both homozygotes). This frequency is not higher than the frequency of diabetes/pre-diabetes observed amongst the overall cohort of patients. Loss-of-function in CEL is not an established mechanism of disease, rather MODY is associated with frameshift mutations resulting in misfolded protein accumulating inside the cell and resulting in apoptosis (PMID: 21784842, 27650499, 34850019) (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Comment:

NM_001807.6(CEL):c.337C>T; p.(Gln113*)- Heterozygous likely benign The p.Gln116* variant in CEL has not been previously reported in individuals with maturity-onset diabetes of the young (MODY). In our internal cohort, this variant was identified in 85 individuals (2 homozygotes), of which 1% were diabetic, 20% pre-diabetic, and 79% healthy (including both homozygotes). This frequency is not higher than the frequency of diabetes/pre-diabetes observed amongst the overall cohort of patients. Loss-of-function in CEL is not an established mechanism of disease, rather MODY is associated with frameshift mutations resulting in misfolded protein accumulating inside the cell and resulting in apoptosis (PMID: 21784842, 27650499, 34850019)

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs1200339761 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jul 15, 2026