ClinVar Genomic variation as it relates to human health
NM_001370259.2(MEN1):c.594G>A (p.Trp198Ter)
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.594G>A (p.Trp198Ter)
Variation ID: 201010 Accession: VCV000201010.8
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11q13.1 11: 64807951 (GRCh38) [ NCBI UCSC ] 11: 64575423 (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 Feb 14, 2024 Jul 13, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001370259.2:c.594G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001357188.2:p.Trp198Ter nonsense NM_000244.4:c.609G>A NP_000235.3:p.Trp203Ter nonsense NM_001370251.2:c.594G>A NP_001357180.2:p.Trp198Ter nonsense NM_001370260.2:c.594G>A NP_001357189.2:p.Trp198Ter nonsense NM_001370261.2:c.594G>A NP_001357190.2:p.Trp198Ter nonsense NM_001370262.2:c.549+45G>A intron variant NM_001370263.2:c.549+45G>A intron variant NM_130799.3:c.594G>A NP_570711.2:p.Trp198Ter nonsense NM_130800.3:c.609G>A NP_570712.2:p.Trp203Ter nonsense NM_130801.3:c.609G>A NP_570713.2:p.Trp203Ter nonsense NM_130802.3:c.609G>A NP_570714.2:p.Trp203Ter nonsense NM_130803.3:c.609G>A NP_570715.2:p.Trp203Ter nonsense NM_130804.3:c.609G>A NP_570716.2:p.Trp203Ter nonsense NC_000011.10:g.64807951C>T NC_000011.9:g.64575423C>T NG_008929.1:g.8344G>A NG_033040.1:g.291G>A LRG_509:g.8344G>A LRG_509t2:c.594G>A LRG_509p2:p.Trp198Ter - Protein change
- W198*, W203*
- Other names
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- Canonical SPDI
- NC_000011.10:64807950: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.
Trans-Omics for Precision Medicine (TOPMed) 0.00000
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 |
2443 | 2460 |
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 (2) |
criteria provided, multiple submitters, no conflicts
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Oct 16, 2022 | RCV000632134.7 | |
Pathogenic (1) |
criteria provided, single submitter
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Jul 13, 2023 | RCV003317132.1 |
Submissions - Germline
Classification
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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
(Sep 10, 2021)
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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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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001983685.1
First in ClinVar: Oct 30, 2021 Last updated: Oct 30, 2021 |
Comment:
Variant summary: MEN1 c.594G>A (p.Trp198X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: MEN1 c.594G>A (p.Trp198X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251392 control chromosomes. c.594G>A has been reported in the literature in multiple individuals affected with Multiple Endocrine Neoplasia Type 1 (example, Chandrasekharappa_1997, Schaaf_2007). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Jul 13, 2023)
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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: SCV000234795.3
First in ClinVar: Jul 05, 2015 Last updated: Jul 29, 2023 |
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of … (more)
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 9215689, 9103196, 9681840, 9929977, 15281352, 9564891, 10551325, 25525159, 33840689, 32552660, 17853334) (less)
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Pathogenic
(Oct 16, 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: SCV000753238.4
First in ClinVar: May 28, 2018 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Trp198*) in the MEN1 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Trp198*) 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). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 201010). This premature translational stop signal has been observed in individual(s) with multiple endocrine neoplasia type 1 (MEN1) (PMID: 9103196, 17853334). This variant is not present in population databases (gnomAD no frequency). (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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Genomic profiling of multiple tissues in two patients with multiple endocrine neoplasia type 1. | Naruoka A | Biomedical research (Tokyo, Japan) | 2021 | PMID: 33840689 |
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 |
Clinical testing for mutations in the MEN1 gene in Sweden: a report on 200 unrelated cases. | Tham E | The Journal of clinical endocrinology and metabolism | 2007 | PMID: 17623761 |
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 |
Analysis of recurrent germline mutations in the MEN1 gene encountered in apparently unrelated families. | Agarwal SK | Human mutation | 1998 | PMID: 9671267 |
Somatic mutations of multiple endocrine neoplasia type 1 gene in the sporadic endocrine tumors. | Shan L | Laboratory investigation; a journal of technical methods and pathology | 1998 | PMID: 9564891 |
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 |
Text-mined citations for rs104894257 ...
HelpRecord last updated Feb 14, 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.