VCV000439894.14 - ClinVar

NM_001370259.2(MEN1):c.939T>G (p.Tyr313Ter)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Pathogenic

3 out of 4 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_001370259.2(MEN1):c.939T>G (p.Tyr313Ter)

Variation ID: 439894 Accession: VCV000439894.14

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 11q13.1 11: 64806342 (GRCh38) [ NCBI UCSC ] 11: 64573814 (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	Sep 30, 2017	Feb 23, 2026	Feb 27, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_001370259.2:c.939T>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001357188.2:p.Tyr313Ter	nonsense
NM_000244.3:c.954T>G
NM_000244.4:c.954T>G	NP_000235.3:p.Tyr318Ter	nonsense
NM_001370251.2:c.939T>G	NP_001357180.2:p.Tyr313Ter	nonsense
NM_001370260.2:c.939T>G	NP_001357189.2:p.Tyr313Ter	nonsense
NM_001370261.2:c.939T>G	NP_001357190.2:p.Tyr313Ter	nonsense
NM_001370262.2:c.834T>G	NP_001357191.2:p.Tyr278Ter	nonsense
NM_001370263.2:c.834T>G	NP_001357192.2:p.Tyr278Ter	nonsense
NM_130799.3:c.939T>G	NP_570711.2:p.Tyr313Ter	nonsense
NM_130800.3:c.954T>G	NP_570712.2:p.Tyr318Ter	nonsense
NM_130801.3:c.954T>G	NP_570713.2:p.Tyr318Ter	nonsense
NM_130802.3:c.954T>G	NP_570714.2:p.Tyr318Ter	nonsense
NM_130803.3:c.954T>G	NP_570715.2:p.Tyr318Ter	nonsense
NM_130804.3:c.954T>G	NP_570716.2:p.Tyr318Ter	nonsense
NC_000011.10:g.64806342A>C
NC_000011.9:g.64573814A>C
NG_008929.1:g.9953T>G
NG_033040.1:g.1900T>G
LRG_509:g.9953T>G
LRG_509t1:c.954T>G
LRG_509t2:c.939T>G

... more HGVS ... less HGVS

Protein change

Y313*, Y318*, Y278*

Other names

Canonical SPDI

NC_000011.10:64806341:A:C

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.

Links

ClinGen: CA381183406 dbSNP: rs1555165128 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.
MEN1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	3129	3150

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.
not specified	Pathogenic (1)	criteria provided, single submitter	Mar 2, 2017	RCV000508282.9
Hereditary cancer-predisposing syndrome	Pathogenic (1)	criteria provided, single submitter	Dec 10, 2021	RCV002376942.2
Multiple endocrine neoplasia, type 1	Pathogenic (1)	criteria provided, single submitter	Feb 27, 2025	RCV003517212.4
MEN1-related disorder	Pathogenic (1)	no assertion criteria provided	Jun 24, 2024	RCV004722849.1

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.
Pathogenic (Mar 02, 2017) C Contributing to aggregate classification	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process)	not specified	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV000604216.1 First in ClinVar: Sep 30, 2017 Last updated: Sep 30, 2017	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 (Dec 10, 2021) C Contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Hereditary cancer-predisposing syndrome	Ambry Genetics Accession: SCV002686414.2 First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024	Publications: PubMed (1) PubMed: 10090472 Comment: show The p.Y313* pathogenic mutation (also known as c.939T>G), located in coding exon 6 of the MEN1 gene, results from a T to G substitution at nucleotide position 939. This changes the amino acid from a tyrosine to a stop codon within coding exon 6. This alteration has been observed in at least one individual with a personal and/or family history that is consistent with MEN1-related disease (Ambry internal data). This alteration has been reported in a cohort of 33 kindreds meeting clinical diagnosis of MEN1 (Mutch MG et al. Hum Mutat, 1999;13:175-85). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less) 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 (Feb 27, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Multiple endocrine neoplasia, type 1	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV004294852.3 First in ClinVar: Feb 14, 2024 Last updated: Feb 23, 2026	Publications: PubMed (3) PubMed: 10090472‚ 12112656‚ 17853334 Comment: show This sequence change creates a premature translational stop signal (p.Tyr313*) in the MEN1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MEN1 are known to be pathogenic (PMID: 12112656, 17853334). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with multiple endocrine neoplasia type 1 (PMID: 10090472). ClinVar contains an entry for this variant (Variation ID: 439894). For these reasons, this variant has been classified as Pathogenic. (less) 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 (Jun 24, 2024) N Not contributing to aggregate classification	no assertion criteria provided	MEN1-related condition	PreventionGenetics, part of Exact Sciences Accession: SCV005339918.1 First in ClinVar: Oct 08, 2024 Last updated: Oct 08, 2024	Comment: show The MEN1 c.954T>G variant is predicted to result in premature protein termination (p.Tyr318*). This variant has been reported in individual(s) with multiple endocrine neoplasia 1 (see for example, kindred 094 in Mutch et al. 1999. PubMed ID: 10090472). This variant has not been reported in a large population database, indicating this variant is rare. This variant is interpreted as pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/439894/). Nonsense variants in MEN1 are expected to be pathogenic. This variant is interpreted as pathogenic. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Comment:

The p.Y313* pathogenic mutation (also known as c.939T>G), located in coding exon 6 of the MEN1 gene, results from a T to G substitution at nucleotide position 939. This changes the amino acid from a tyrosine to a stop codon within coding exon 6. This alteration has been observed in at least one individual with a personal and/or family history that is consistent with MEN1-related disease (Ambry internal data). This alteration has been reported in a cohort of 33 kindreds meeting clinical diagnosis of MEN1 (Mutch MG et al. Hum Mutat, 1999;13:175-85). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

Comment:

This sequence change creates a premature translational stop signal (p.Tyr313*) in the MEN1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MEN1 are known to be pathogenic (PMID: 12112656, 17853334). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with multiple endocrine neoplasia type 1 (PMID: 10090472). ClinVar contains an entry for this variant (Variation ID: 439894). For these reasons, this variant has been classified as Pathogenic.

Comment:

The MEN1 c.954T>G variant is predicted to result in premature protein termination (p.Tyr318*). This variant has been reported in individual(s) with multiple endocrine neoplasia 1 (see for example, kindred 094 in Mutch et al. 1999. PubMed ID: 10090472). This variant has not been reported in a large population database, indicating this variant is rare. This variant is interpreted as pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/439894/). Nonsense variants in MEN1 are expected to be pathogenic. This variant is interpreted as pathogenic.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Developing effective screening strategies in multiple endocrine neoplasia type 1 (MEN 1) on the basis of clinical and sequencing data of German patients with MEN 1.	Schaaf L	Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association	2007	PMID: 17853334
Germline mutation profile of MEN1 in multiple endocrine neoplasia type 1: search for correlation between phenotype and the functional domains of the MEN1 protein.	Wautot V	Human mutation	2002	PMID: 12112656
Germline mutations in the multiple endocrine neoplasia type 1 gene: evidence for frequent splicing defects.	Mutch MG	Human mutation	1999	PMID: 10090472

Text-mined citations for rs1555165128 ...

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 Apr 13, 2026