ClinVar Genomic variation as it relates to human health
NM_001370259.2(MEN1):c.1296G>A (p.Leu432=)
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.
Uncertain significance(1); Benign(9); Likely benign(4)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_001370259.2(MEN1):c.1296G>A (p.Leu432=)
Variation ID: 36524 Accession: VCV000036524.60
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 11q13.1 11: 64805088 (GRCh38) [ NCBI UCSC ] 11: 64572560 (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 Dec 29, 2015 May 1, 2024 Mar 1, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_001370259.2:c.1296G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001357188.2:p.Leu432= synonymous NM_000244.4:c.1311G>A NP_000235.3:p.Leu437= synonymous NM_001370251.2:c.1422G>A NP_001357180.2:p.Leu474= synonymous NM_001370260.2:c.1296G>A NP_001357189.2:p.Leu432= synonymous NM_001370261.2:c.1296G>A NP_001357190.2:p.Leu432= synonymous NM_001370262.2:c.1191G>A NP_001357191.2:p.Leu397= synonymous NM_001370263.2:c.1191G>A NP_001357192.2:p.Leu397= synonymous NM_130799.3:c.1296G>A NP_570711.2:p.Leu432= synonymous NM_130800.3:c.1311G>A NP_570712.2:p.Leu437= synonymous NM_130801.3:c.1311G>A NP_570713.2:p.Leu437= synonymous NM_130802.3:c.1311G>A NP_570714.2:p.Leu437= synonymous NM_130803.3:c.1311G>A NP_570715.2:p.Leu437= synonymous NM_130804.3:c.1311G>A NP_570716.2:p.Leu437= synonymous NC_000011.10:g.64805088C>T NC_000011.9:g.64572560C>T NG_008929.1:g.11207G>A NG_033040.1:g.3154G>A LRG_509:g.11207G>A LRG_509t1:c.1311G>A LRG_509p1:p.Leu437= LRG_509t2:c.1296G>A LRG_509p2:p.Leu432= - Protein change
- Other names
- -
- Canonical SPDI
- NC_000011.10:64805087:C:T
-
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.
-
0.00080 (T)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 30x 0.00062
1000 Genomes Project 0.00080
Exome Aggregation Consortium (ExAC) 0.00102
The Genome Aggregation Database (gnomAD), exomes 0.00115
The Genome Aggregation Database (gnomAD) 0.00119
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00131
Trans-Omics for Precision Medicine (TOPMed) 0.00144
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 |
2443 | 2460 |
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. |
---|---|---|---|---|
Benign (3) |
criteria provided, multiple submitters, no conflicts
|
Feb 1, 2024 | RCV000030197.23 | |
Benign/Likely benign (2) |
criteria provided, multiple submitters, no conflicts
|
Apr 2, 2021 | RCV000492032.5 | |
Benign (4) |
criteria provided, single submitter
|
Mar 1, 2024 | RCV000679247.32 | |
Benign/Likely benign (6) |
criteria provided, multiple submitters, no conflicts
|
Aug 15, 2023 | RCV000379404.21 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Jan 13, 2018 | RCV000353672.7 | |
Benign (1) |
criteria provided, single submitter
|
Mar 30, 2021 | RCV003891445.1 |
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. |
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. |
|
---|---|---|---|---|---|
Benign
(Aug 15, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000604200.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Likely benign
(May 26, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000341629.4
First in ClinVar: Dec 06, 2016 Last updated: May 03, 2018 |
Number of individuals with the variant: 1
Sex: mixed
|
|
Uncertain significance
(Jan 13, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Hyperparathyroidism
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000373094.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (less)
|
|
Benign
(Jan 13, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Multiple endocrine neoplasia, type 1
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000373093.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
|
|
Benign
(Oct 20, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002014999.2
First in ClinVar: Nov 20, 2021 Last updated: Jun 24, 2023 |
|
|
Likely benign
(Jan 25, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: no
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV002066183.1
First in ClinVar: Jan 29, 2022 Last updated: Jan 29, 2022 |
|
|
Benign
(Apr 02, 2021)
|
criteria provided, single submitter
Method: curation
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Sema4, Sema4
Accession: SCV002530048.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022 |
|
|
Benign
(Sep 20, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Multiple endocrine neoplasia, type 1
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV004359144.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
|
|
Benign
(Mar 30, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
MEN1-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000805917.2
First in ClinVar: Sep 14, 2018 Last updated: Mar 16, 2024 |
Comment:
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
|
|
Benign
(Mar 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001148321.21
First in ClinVar: Feb 03, 2020 Last updated: Apr 15, 2024 |
Comment:
MEN1: BP4, BS1, BS2
Number of individuals with the variant: 15
|
|
Likely benign
(Jul 31, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000579663.6
First in ClinVar: Jun 25, 2017 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
|
|
Benign
(Jun 03, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000513596.4
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
|
|
Likely benign
(Aug 15, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV002549976.4
First in ClinVar: Jul 27, 2022 Last updated: Aug 18, 2023 |
|
|
Benign
(Feb 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Multiple endocrine neoplasia, type 1
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000153858.13
First in ClinVar: Jun 09, 2014 Last updated: Feb 20, 2024 |
|
|
Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001744463.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
|
|
Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001972977.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
|
|
Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001958005.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
|
|
click to load more click to collapse |
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 |
---|---|---|---|---|
Multiple endocrine neoplasia type 1 (MEN1) and type 4 (MEN4). | Thakker RV | Molecular and cellular endocrinology | 2014 | PMID: 23933118 |
Multiple endocrine neoplasia type 1 (MEN1). | Thakker RV | Best practice & research. Clinical endocrinology & metabolism | 2010 | PMID: 20833329 |
Multiple endocrine neoplasia type 1 (MEN1): analysis of 1336 mutations reported in the first decade following identification of the gene. | Lemos MC | Human mutation | 2008 | PMID: 17879353 |
MEN1 gene mutations in Hungarian patients with multiple endocrine neoplasia type 1. | Balogh K | Clinical endocrinology | 2007 | PMID: 17953629 |
Age-related penetrance of endocrine tumours in multiple endocrine neoplasia type 1 (MEN1): a multicentre study of 258 gene carriers. | Machens A | Clinical endocrinology | 2007 | PMID: 17590169 |
Characteristics of the Danish families with multiple endocrine neoplasia type 1. | Jäger AC | Molecular and cellular endocrinology | 2006 | PMID: 16563611 |
Genetic screening methods for the detection of mutations responsible for multiple endocrine neoplasia type 1. | Balogh K | Molecular genetics and metabolism | 2004 | PMID: 15464422 |
Recent advances in MEN1 gene study for pituitary tumor pathogenesis. | Kameya T | Frontiers of hormone research | 2004 | PMID: 15281352 |
Unusual presentation of multiple endocrine neoplasia type 1 in a young woman with a novel mutation of the MEN1 gene. | Balogh K | Journal of human genetics | 2004 | PMID: 15205994 |
10 Swiss kindreds with multiple endocrine neoplasia type 1: assessment of screening methods. | Clerici T | Swiss medical weekly | 2001 | PMID: 11524904 |
Molecular pathology of multiple endocrine neoplasia type I: two novel germline mutations and updated classification of mutations affecting MEN1 gene. | Martín-Campos JM | Diagnostic molecular pathology : the American journal of surgical pathology, part B | 1999 | PMID: 10617276 |
MEN1 gene mutation analysis of sporadic adrenocortical lesions. | Görtz B | International journal of cancer | 1999 | PMID: 9935177 |
Mutation analysis of the MEN1 gene in Belgian patients with multiple endocrine neoplasia type 1 and related diseases. | Poncin J | Human mutation | 1999 | PMID: 9888389 |
Germline mutations of the MEN1 gene in familial multiple endocrine neoplasia type 1 and related states. | Agarwal SK | Human molecular genetics | 1997 | PMID: 9215689 |
Positional cloning of the gene for multiple endocrine neoplasia-type 1. | Chandrasekharappa SC | Science (New York, N.Y.) | 1997 | PMID: 9103196 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=MEN1 | - | - | - | - |
click to load more click to collapse |
Text-mined citations for rs138770431 ...
HelpRecord last updated May 01, 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.