This sequence change creates a premature translational stop signal (p.Trp265Glyfs*16) 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MEN1-related conditions. RNA analysis provides insufficient evidence to determine the effect of this variant on MEN1 splicing (Invitae). For these reasons, this variant has been classified as Pathogenic.
ClinVar Genomic variation as it relates to human health
NM_001370259.2(MEN1):c.792del (p.Trp265fs)
Germline
Classification
Help
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.
(1)
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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.
Pathogenic
1
criteria provided, single submitter
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001370259.2(MEN1):c.792del (p.Trp265fs)
Variation ID: 2694618 Accession: VCV002694618.1
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 11q13.1 11: 64807211 (GRCh38) [ NCBI UCSC ] 11: 64574683 (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 Feb 14, 2024 Feb 14, 2024 Nov 10, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001370259.2:c.792del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001357188.2:p.Trp265fs frameshift NM_000244.4:c.807del NP_000235.3:p.Trp270fs frameshift NM_001370251.2:c.792del NP_001357180.2:p.Trp265fs frameshift NM_001370260.2:c.792del NP_001357189.2:p.Trp265fs frameshift NM_001370261.2:c.792del NP_001357190.2:p.Trp265fs frameshift NM_001370262.2:c.687del NP_001357191.2:p.Trp230fs frameshift NM_001370263.2:c.687del NP_001357192.2:p.Trp230fs frameshift NM_001407142.1:c.792del NP_001394071.1:p.Trp265fs frameshift NM_001407143.1:c.792del NP_001394072.1:p.Trp265fs frameshift NM_001407144.1:c.792del NP_001394073.1:p.Trp265fs frameshift NM_001407145.1:c.807del NP_001394074.1:p.Trp270fs frameshift NM_001407146.1:c.792del NP_001394075.1:p.Trp265fs frameshift NM_001407147.1:c.792del NP_001394076.1:p.Trp265fs frameshift NM_001407148.1:c.687del NP_001394077.1:p.Trp230fs frameshift NM_001407149.1:c.687del NP_001394078.1:p.Trp230fs frameshift NM_001407150.1:c.807del NP_001394079.1:p.Trp270fs frameshift NM_001407151.1:c.687del NP_001394080.1:p.Trp230fs frameshift NM_001407152.1:c.792del NP_001394081.1:p.Trp265fs frameshift NM_130799.3:c.792del NP_570711.2:p.Trp265fs frameshift NM_130800.3:c.807del NP_570712.2:p.Trp270fs frameshift NM_130801.3:c.807del NP_570713.2:p.Trp270fs frameshift NM_130802.3:c.807del NP_570714.2:p.Trp270fs frameshift NM_130803.3:c.807del NP_570715.2:p.Trp270fs frameshift NM_130804.3:c.807del NP_570716.2:p.Trp270fs frameshift NR_176284.1:n.841del non-coding transcript variant NR_176285.1:n.853del non-coding transcript variant NR_176286.1:n.856del non-coding transcript variant NR_176287.1:n.1114del non-coding transcript variant NC_000011.10:g.64807211del NC_000011.9:g.64574683del NG_008929.1:g.9084del NG_033040.1:g.1031del NG_033040.2:g.1003del LRG_509:g.9084del LRG_509t1:c.807del LRG_509p1:p.Trp270Glyfs LRG_509t2:c.792del LRG_509p2:p.Trp265Glyfs - Protein change
- W230fs, W265fs, W270fs
- Other names
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- Canonical SPDI
- NC_000011.10:64807210:G:
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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
Help
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
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. |
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| MEN1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
2580 | 2601 | |
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. |
|---|---|---|---|---|
| Pathogenic (1) |
criteria provided, single submitter
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Nov 10, 2023 | RCV003517557.2 |
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. |
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Pathogenic
(Nov 10, 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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV004248436.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Trp265Glyfs*16) 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.Trp265Glyfs*16) 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MEN1-related conditions. RNA analysis provides insufficient evidence to determine the effect of this variant on MEN1 splicing (Invitae). For these reasons, this variant has been classified as Pathogenic. (less)
|
Comment:
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. |
Comment:
This sequence change creates a premature translational stop signal (p.Trp265Glyfs*16) 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MEN1-related conditions. RNA analysis provides insufficient evidence to determine the effect of this variant on MEN1 splicing (Invitae). For these reasons, this variant has been classified as Pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| 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 |
| 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 |
Text-mined citations for this variant ...
HelpRecord last updated Sep 30, 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.