ClinVar Genomic variation as it relates to human health
NM_001370259.2(MEN1):c.1049+1G>A
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.1049+1G>A
Variation ID: 527268 Accession: VCV000527268.13
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11q13.1 11: 64806231 (GRCh38) [ NCBI UCSC ] 11: 64573703 (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 28, 2018 May 1, 2024 Aug 9, 2022 - HGVS
- ... more HGVS ... less HGVS
- Protein change
- Other names
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- Canonical SPDI
- NC_000011.10:64806230:C:T
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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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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
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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 |
2521 | 2538 |
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 (2) |
criteria provided, multiple submitters, no conflicts
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Aug 9, 2022 | RCV000632121.9 | |
Pathogenic (1) |
criteria provided, single submitter
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Nov 29, 2018 | RCV002404747.2 | |
not provided (1) |
no classification provided
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- | RCV003330850.1 |
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
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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
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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:
unknown
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Baylor Genetics
Accession: SCV004192442.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Jan 27, 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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Invitae
Accession: SCV000753225.6
First in ClinVar: May 28, 2018 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this … (more)
For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 527268). This variant is also known as nt 6024. Disruption of this splice site has been observed in individual(s) with multiple endocrine neoplasia type 1 (PMID: 9463336, 11836268). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 7 of the MEN1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MEN1 are known to be pathogenic (PMID: 12112656, 17853334). (less)
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Pathogenic
(Nov 29, 2018)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002707900.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The c.1049+1G>A intronic pathogenic mutation results from a G to A substitution one nucleotide after coding exon 6 of the MEN1 gene. This mutation was … (more)
The c.1049+1G>A intronic pathogenic mutation results from a G to A substitution one nucleotide after coding exon 6 of the MEN1 gene. This mutation was seen in a patient with parathyroid, pancreatic, and pituitary tumors (Bassett JH et al. Am. J. Hum. Genet., 1998 Feb;62:232-44). In addition to the clinical data presented in the literature, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as a disease-causing mutation. (less)
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not provided
(-)
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no classification provided
Method: phenotyping only
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Multiple endocrine neoplasia
Affected status: unknown
Allele origin:
unknown
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GenomeConnect - Invitae Patient Insights Network
Accession: SCV004037533.1
First in ClinVar: Oct 07, 2023 Last updated: Oct 07, 2023 |
Comment:
Variant classified as Pathogenic and reported on 06-13-2019 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report … (more)
Variant classified as Pathogenic and reported on 06-13-2019 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. (less)
Clinical Features:
Family history of cancer (present)
Indication for testing: Diagnostic
Age: 20-29 years
Sex: male
Method: Gene Panel Sequencing
Testing laboratory: Invitae
Date variant was reported to submitter: 2019-06-13
Testing laboratory interpretation: Pathogenic
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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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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 |
Splicing in action: assessing disease causing sequence changes. | Baralle D | Journal of medical genetics | 2005 | PMID: 16199547 |
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 |
Pituitary disease in MEN type 1 (MEN1): data from the France-Belgium MEN1 multicenter study. | Vergès B | The Journal of clinical endocrinology and metabolism | 2002 | PMID: 11836268 |
Characterization of mutations in patients with multiple endocrine neoplasia type 1. | Bassett JH | American journal of human genetics | 1998 | PMID: 9463336 |
Text-mined citations for rs1114167489 ...
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.