ClinVar Genomic variation as it relates to human health
NM_001370259.2(MEN1):c.1271AGG[1] (p.Glu425del)
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001370259.2(MEN1):c.1271AGG[1] (p.Glu425del)
Variation ID: 1067928 Accession: VCV001067928.10
- Type and length
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Microsatellite, 3 bp
- Location
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Cytogenetic: 11q13.1 11: 64805108-64805110 (GRCh38) [ NCBI UCSC ] 11: 64572580-64572582 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 May 10, 2021 Feb 20, 2024 Nov 14, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001370259.2:c.1271AGG[1] MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001357188.2:p.Glu425del inframe deletion NM_000244.4:c.1286AGG[1] NP_000235.3:p.Glu430del inframe deletion NM_001370251.2:c.1397AGG[1] NP_001357180.2:p.Glu467del inframe deletion NM_001370260.2:c.1271AGG[1] NP_001357189.2:p.Glu425del inframe deletion NM_001370261.2:c.1271AGG[1] NP_001357190.2:p.Glu425del inframe deletion NM_001370262.2:c.1166AGG[1] NP_001357191.2:p.Glu390del inframe deletion NM_001370263.2:c.1166AGG[1] NP_001357192.2:p.Glu390del inframe deletion NM_130799.2:c.1274_1276del inframe deletion NM_130799.3:c.1271AGG[1] NP_570711.2:p.Glu425del inframe deletion NM_130800.3:c.1286AGG[1] NP_570712.2:p.Glu430del inframe deletion NM_130801.3:c.1286AGG[1] NP_570713.2:p.Glu430del inframe deletion NM_130802.3:c.1286AGG[1] NP_570714.2:p.Glu430del inframe deletion NM_130803.3:c.1286AGG[1] NP_570715.2:p.Glu430del inframe deletion NM_130804.3:c.1286AGG[1] NP_570716.2:p.Glu430del inframe deletion NC_000011.10:g.64805110TCC[1] NC_000011.9:g.64572582TCC[1] NG_008929.1:g.11182AGG[1] NG_033040.1:g.3129AGG[1] LRG_509:g.11182AGG[1] - Protein change
- E390del, E425del, E430del, E467del
- Other names
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- Canonical SPDI
- NC_000011.10:64805107:CCTCCTCC:CCTCC
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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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. |
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MEN1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
2578 | 2599 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (1) |
criteria provided, single submitter
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Aug 9, 2022 | RCV001379321.8 | |
Pathogenic/Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Nov 14, 2023 | RCV002225831.4 |
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
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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. |
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Pathogenic
(Aug 09, 2022)
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criteria provided, single submitter
Method: clinical testing
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Multiple endocrine neoplasia, type 1
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001577107.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this variant affects MEN1 function (PMID: 17184987, 18310289). Algorithms developed … (more)
For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this variant affects MEN1 function (PMID: 17184987, 18310289). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 1067928). This variant is also known as 1384delAGG. This variant has been observed in individuals with clinical features of multiple endocrine neoplasia type 1 (PMID: 9683585, 10762295, 12112656; Invitae; External communication). This variant is not present in population databases (gnomAD no frequency). This variant, c.1274_1276del, results in the deletion of 1 amino acid(s) of the MEN1 protein (p.Glu425del), but otherwise preserves the integrity of the reading frame. (less)
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Likely pathogenic
(Apr 08, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV002504198.2
First in ClinVar: Apr 30, 2022 Last updated: Mar 04, 2023 |
Comment:
Not observed at significant frequency in large population cohorts (gnomAD); In-frame deletion of 1 amino acid in a non-repeat region; In silico analysis supports a … (more)
Not observed at significant frequency in large population cohorts (gnomAD); In-frame deletion of 1 amino acid in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; Published functional studies demonstrate a damaging effect: lack of cell growth inhibition, reduced menin expression, and impaired menin function (Hussein 2007, Hussein 2008); Observed in an individual with a personal and family history of MEN1-associated lesions in published literature (Giraud 1998).; This variant is associated with the following publications: (PMID: 17879353, 10730900, 10762295, 11836268, 9683585, 18310289, 12112656, 17184987, 9989505) (less)
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Pathogenic
(Nov 14, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV004564588.1
First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024 |
Comment:
The MEN1 c.1274_1276del; p.Glu425del variant (rs2136101303) is reported in the literature in multiple individuals affected with multiple endocrine neoplasia type 1 (Giraud 1998, Wautot 2002). … (more)
The MEN1 c.1274_1276del; p.Glu425del variant (rs2136101303) is reported in the literature in multiple individuals affected with multiple endocrine neoplasia type 1 (Giraud 1998, Wautot 2002). This variant is also reported in ClinVar (Variation ID: 1067928) and is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. Functional analyses of the variant protein show reduced menin function (Hussein 2008). This variant deletes a single glutamic acid residue leaving the rest of the protein in-frame. Based on available information, this variant is considered to be pathogenic. References: Giraud S et al. Germ-line mutation analysis in patients with multiple endocrine neoplasia type 1 and related disorders. Am J Hum Genet. 1998 Aug;63(2):455-67. PMID: 9683585. Hussein N et al. Deregulation of anti-Mullerian hormone/BMP and transforming growth factor-beta pathways in Leydig cell lesions developed in male heterozygous multiple endocrine neoplasia type 1 mutant mice. Endocr Relat Cancer. 2008 Mar;15(1):217-27. PMID: 18310289. Wautot V et al. Germline mutation profile of MEN1 in multiple endocrine neoplasia type 1: search for correlation between phenotype and the functional domains of the MEN1 protein. Hum Mutat. 2002 Jul;20(1):35-47. PMID: 12112656. (less)
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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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Deregulation of anti-Mullerian hormone/BMP and transforming growth factor-beta pathways in Leydig cell lesions developed in male heterozygous multiple endocrine neoplasia type 1 mutant mice. | Hussein N | Endocrine-related cancer | 2008 | PMID: 18310289 |
Reconstituted expression of menin in Men1-deficient mouse Leydig tumour cells induces cell cycle arrest and apoptosis. | Hussein N | European journal of cancer (Oxford, England : 1990) | 2007 | PMID: 17184987 |
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 |
Clinical features of multiple endocrine neoplasia type 1 (MEN1) phenocopy without germline MEN1 gene mutations: analysis of 20 Japanese sporadic cases with MEN1. | Hai N | Clinical endocrinology | 2000 | PMID: 10762295 |
Germ-line mutation analysis in patients with multiple endocrine neoplasia type 1 and related disorders. | Giraud S | American journal of human genetics | 1998 | PMID: 9683585 |
Text-mined citations for rs2136101303 ...
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.