For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with MEN1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu280*) 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).
ClinVar Genomic variation as it relates to human health
NM_001370259.2(MEN1):c.837del (p.Ala279_Leu280insTer)
Germline
Classification
Help
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.
(1)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Pathogenic
1
criteria provided, single submitter
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_001370259.2(MEN1):c.837del (p.Ala279_Leu280insTer)
Variation ID: 2114088 Accession: VCV002114088.2
- Type and length
-
Deletion, 1 bp
- Location
-
Cytogenetic: 11q13.1 11: 64807086 (GRCh38) [ NCBI UCSC ] 11: 64574558 (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 Feb 8, 2023 Feb 20, 2024 Mar 19, 2022 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001370259.2:c.837del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001357188.2:p.Ala279_Leu280insTer frameshift NM_000244.4:c.852del NP_000235.3:p.Ala284_Leu285insTer frameshift NM_001370251.2:c.837del NP_001357180.2:p.Ala279_Leu280insTer frameshift NM_001370260.2:c.837del NP_001357189.2:p.Ala279_Leu280insTer frameshift NM_001370261.2:c.837del NP_001357190.2:p.Ala279_Leu280insTer frameshift NM_001370262.2:c.732del NP_001357191.2:p.Ala244_Leu245insTer frameshift NM_001370263.2:c.732del NP_001357192.2:p.Ala244_Leu245insTer frameshift NM_001407142.1:c.836delC NP_001394071.1:p.Leu280Terfs frameshift nonsense NM_001407143.1:c.836delC NP_001394072.1:p.Leu280Terfs frameshift nonsense NM_001407144.1:c.836delC NP_001394073.1:p.Leu280Terfs frameshift nonsense NM_001407145.1:c.851delC NP_001394074.1:p.Leu285Terfs frameshift nonsense NM_001407146.1:c.836delC NP_001394075.1:p.Leu280Terfs frameshift nonsense NM_001407147.1:c.836delC NP_001394076.1:p.Leu280Terfs frameshift nonsense NM_001407148.1:c.731delC NP_001394077.1:p.Leu245Terfs frameshift nonsense NM_001407149.1:c.731delC NP_001394078.1:p.Leu245Terfs frameshift nonsense NM_001407150.1:c.851delC NP_001394079.1:p.Leu285Terfs frameshift nonsense NM_001407151.1:c.731delC NP_001394080.1:p.Leu245Terfs frameshift nonsense NM_001407152.1:c.836delC NP_001394081.1:p.Leu280Terfs frameshift nonsense NM_130799.3:c.837del NP_570711.2:p.Ala279_Leu280insTer frameshift NM_130800.3:c.852del NP_570712.2:p.Ala284_Leu285insTer frameshift NM_130801.3:c.852del NP_570713.2:p.Ala284_Leu285insTer frameshift NM_130802.3:c.852del NP_570714.2:p.Ala284_Leu285insTer frameshift NM_130803.3:c.852del NP_570715.2:p.Ala284_Leu285insTer frameshift NM_130804.3:c.852del NP_570716.2:p.Ala284_Leu285insTer frameshift NR_176284.1:n.885delC NR_176285.1:n.897delC NR_176286.1:n.900delC NR_176287.1:n.1158delC NC_000011.10:g.64807087del NC_000011.9:g.64574559del NG_008929.1:g.9209del NG_033040.1:g.1156del NG_033040.2:g.1128del LRG_509:g.9209del LRG_509t1:c.851del LRG_509p1:p.Leu285Terfs LRG_509t2:c.836del LRG_509p2:p.Leu280Terfs - Protein change
- -
- Other names
- -
- Canonical SPDI
- NC_000011.10:64807085:GG:G
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe 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
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 | ||
|---|---|---|---|---|---|---|
| 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 |
2580 | 2601 | |
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. |
|---|---|---|---|---|
| Pathogenic (1) |
criteria provided, single submitter
|
Mar 19, 2022 | RCV003029869.3 |
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. |
More information
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 19, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Multiple endocrine neoplasia, type 1
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV003332660.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 20, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with MEN1-related conditions. … (more)
For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with MEN1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu280*) 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). (less)
|
Comment:
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with MEN1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu280*) 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).
Citations for germline classification of this variant
Help| 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 |
Text-mined citations for this variant ...
HelpRecord last updated Sep 29, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.