ClinVar Genomic variation as it relates to human health
NM_001370259.2(MEN1):c.1533_1534dup (p.Ser512fs)
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.1533_1534dup (p.Ser512fs)
Variation ID: 201021 Accession: VCV000201021.12
- Type and length
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Microsatellite, 2 bp
- Location
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Cytogenetic: 11q13.1 11: 64804632-64804633 (GRCh38) [ NCBI UCSC ] 11: 64572104-64572105 (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 Jul 5, 2015 Feb 14, 2024 May 22, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001370259.2:c.1533_1534dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001357188.2:p.Ser512fs frameshift NM_000244.4:c.1548_1549dup NP_000235.3:p.Ser517fs frameshift NM_001370251.2:c.1659_1660dup NP_001357180.2:p.Ser554fs frameshift NM_001370260.2:c.1533_1534dup NP_001357189.2:p.Ser512fs frameshift NM_001370261.2:c.1533_1534dup NP_001357190.2:p.Ser512fs frameshift NM_001370262.2:c.1428_1429dup NP_001357191.2:p.Ser477fs frameshift NM_001370263.2:c.1428_1429dup NP_001357192.2:p.Ser477fs frameshift NM_130799.2:c.1533_1534dupGT frameshift NM_130799.3:c.1533_1534dup NP_570711.2:p.Ser512fs frameshift NM_130800.3:c.1548_1549dup NP_570712.2:p.Ser517fs frameshift NM_130801.3:c.1548_1549dup NP_570713.2:p.Ser517fs frameshift NM_130802.3:c.1548_1549dup NP_570714.2:p.Ser517fs frameshift NM_130803.3:c.1548_1549dup NP_570715.2:p.Ser517fs frameshift NM_130804.3:c.1548_1549dup NP_570716.2:p.Ser517fs frameshift NC_000011.10:g.64804633AC[3] NC_000011.9:g.64572105AC[3] NG_008929.1:g.11659GT[3] NG_033040.1:g.3606GT[3] LRG_509:g.11659GT[3] - Protein change
- S512fs, S477fs, S517fs, S554fs
- Other names
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- Canonical SPDI
- NC_000011.10:64804632:ACAC:ACACAC
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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 |
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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
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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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Oct 8, 2013 | RCV000182462.2 | |
Pathogenic (1) |
criteria provided, single submitter
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Apr 6, 2022 | RCV000491410.3 | |
Pathogenic (1) |
criteria provided, single submitter
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May 22, 2023 | RCV001382418.7 |
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
(Oct 08, 2013)
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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: SCV000234807.2
First in ClinVar: Jul 05, 2015 Last updated: Jul 05, 2015 |
Comment:
The c.1533_1534dupGT mutation in the MEN1 gene causes a frameshift starting with codon Serine 512, changes this amino acid to a Cysteine residue and creates … (more)
The c.1533_1534dupGT mutation in the MEN1 gene causes a frameshift starting with codon Serine 512, changes this amino acid to a Cysteine residue and creates a premature Stop codon at position 48 of the new reading frame, denoted p.Ser512CysfsX48. The normal sequence with the bases that are inserted in braces is: GTGT{GT}CAGG. This mutation is predicted to cause loss of normal protein function through protein truncation. Specifically, the last 99 residues are lost and replaced by 47 incorrect residues. Although this mutation has not been previously reported to our knowledge, its presence is consistent with a diagnosis of multiple endocrine neoplasia type 1. The variant is found in MEN1 panel(s). (less)
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Pathogenic
(Apr 06, 2022)
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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: SCV000579710.5
First in ClinVar: Jun 25, 2017 Last updated: Nov 29, 2022 |
Comment:
The c.1533_1534dupGT pathogenic mutation, located in coding exon 9 of the MEN1 gene, results from a duplication of GT at nucleotide position 1533, causing a … (more)
The c.1533_1534dupGT pathogenic mutation, located in coding exon 9 of the MEN1 gene, results from a duplication of GT at nucleotide position 1533, causing a translational frameshift with a predicted alternate stop codon (p.S512Cfs*48). This alteration occurs at the 3' terminus of theMEN1 gene, is not expected to trigger nonsense-mediated mRNA decay, and impacts the last 99 amino acids of the protein. However, premature stop codons are typically deleterious in nature and the impacted region is critical for protein function (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. (less)
Number of individuals with the variant: 1
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Pathogenic
(May 22, 2023)
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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: SCV001581173.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the MEN1 protein in which other variant(s) (p.Arg516Glyfs*43) have … (more)
For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the MEN1 protein in which other variant(s) (p.Arg516Glyfs*43) have been determined to be pathogenic (PMID: 9215689, 12112656, 12213668, 15670192, 17065424, 17853334, 23321498). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 201021). 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.Ser512Cysfs*48) in the MEN1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 99 amino acid(s) of the MEN1 protein. (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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Genetic analysis in young patients with sporadic pituitary macroadenomas: besides AIP don't forget MEN1 genetic analysis. | Cuny T | European journal of endocrinology | 2013 | PMID: 23321498 |
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 |
Rapid mutation screening for HRPT2 and MEN1 mutations associated with familial and sporadic primary hyperparathyroidism. | Howell VM | The Journal of molecular diagnostics : JMD | 2006 | PMID: 17065424 |
Detection of an MEN1 gene mutation depends on clinical features and supports current referral criteria for diagnostic molecular genetic testing. | Ellard S | Clinical endocrinology | 2005 | PMID: 15670192 |
Involvement of the MEN1 gene locus in familial isolated hyperparathyroidism. | Villablanca A | European journal of endocrinology | 2002 | PMID: 12213668 |
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 of the MEN1 gene in familial multiple endocrine neoplasia type 1 and related states. | Agarwal SK | Human molecular genetics | 1997 | PMID: 9215689 |
Text-mined citations for rs794728659 ...
HelpRecord last updated Feb 20, 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.