This variant disrupts a region of the MEN1 protein in which other variant(s) (p.Glln578*) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This sequence change creates a premature translational stop signal (p.Lys569Aspfs*27) in the MEN1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 42 amino acid(s) of the MEN1 protein. 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. This variant disrupts the NLS2 domain of the MEN1 protein, which is important for DNA binding and repression of cell proliferation (PMID: 15331604, 16449969). While functional studies have not been performed to directly test the effect of this variant on MEN1 protein function, this suggests that disruption of this region of the protein is causative of disease. For these reasons, this variant has been classified as Pathogenic.
ClinVar Genomic variation as it relates to human health
NM_001370259.2(MEN1):c.1705_1706del (p.Lys569fs)
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)
Help
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.1705_1706del (p.Lys569fs)
Variation ID: 2863013 Accession: VCV002863013.1
- Type and length
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Deletion, 2 bp
- Location
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Cytogenetic: 11q13.1 11: 64804461-64804462 (GRCh38) [ NCBI UCSC ] 11: 64571933-64571934 (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 20, 2024 Feb 20, 2024 Jul 25, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001370259.2:c.1705_1706del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001357188.2:p.Lys569fs frameshift NM_000244.4:c.1720_1721del NP_000235.3:p.Lys574fs frameshift NM_001370251.2:c.1831_1832del NP_001357180.2:p.Lys611fs frameshift NM_001370260.2:c.1705_1706del NP_001357189.2:p.Lys569fs frameshift NM_001370261.2:c.1705_1706del NP_001357190.2:p.Lys569fs frameshift NM_001370262.2:c.1600_1601del NP_001357191.2:p.Lys534fs frameshift NM_001370263.2:c.1600_1601del NP_001357192.2:p.Lys534fs frameshift NM_001407142.1:c.1831_1832del NP_001394071.1:p.Lys611fs frameshift NM_001407143.1:c.1831_1832del NP_001394072.1:p.Lys611fs frameshift NM_001407144.1:c.1831_1832del NP_001394073.1:p.Lys611fs frameshift NM_001407145.1:c.1720_1721del NP_001394074.1:p.Lys574fs frameshift NM_001407146.1:c.1705_1706del NP_001394075.1:p.Lys569fs frameshift NM_001407147.1:c.1705_1706del NP_001394076.1:p.Lys569fs frameshift NM_001407148.1:c.1600_1601del NP_001394077.1:p.Lys534fs frameshift NM_001407149.1:c.1600_1601del NP_001394078.1:p.Lys534fs frameshift NM_001407150.1:c.1846_1847del NP_001394079.1:p.Lys616fs frameshift NM_001407151.1:c.1726_1727del NP_001394080.1:p.Lys576fs frameshift NM_001407152.1:c.1540_1541del NP_001394081.1:p.Lys514fs frameshift NM_130799.3:c.1705_1706del NP_570711.2:p.Lys569fs frameshift NM_130800.3:c.1720_1721del NP_570712.2:p.Lys574fs frameshift NM_130801.3:c.1720_1721del NP_570713.2:p.Lys574fs frameshift NM_130802.3:c.1720_1721del NP_570714.2:p.Lys574fs frameshift NM_130803.3:c.1720_1721del NP_570715.2:p.Lys574fs frameshift NM_130804.3:c.1720_1721del NP_570716.2:p.Lys574fs frameshift NR_176284.1:n.1903_1904del non-coding transcript variant NR_176285.1:n.1915_1916del non-coding transcript variant NR_176286.1:n.1918_1919del non-coding transcript variant NR_176287.1:n.2176_2177del non-coding transcript variant NC_000011.10:g.64804461_64804462del NC_000011.9:g.64571933_64571934del NG_008929.1:g.11833_11834del NG_033040.1:g.3780_3781del NG_033040.2:g.3752_3753del LRG_509:g.11833_11834del LRG_509t1:c.1720_1721del LRG_509p1:p.Lys574Aspfs LRG_509t2:c.1705_1706del LRG_509p2:p.Lys569Aspfs - Protein change
- K534fs, K574fs, K616fs, K576fs, K514fs, K569fs, K611fs
- Other names
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- Canonical SPDI
- NC_000011.10:64804460:TT:
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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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Jul 25, 2023 | RCV003632237.3 |
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
(Jul 25, 2023)
|
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: SCV004463384.1
First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024 |
Comment:
This variant disrupts a region of the MEN1 protein in which other variant(s) (p.Glln578*) have been determined to be pathogenic (Invitae). This suggests that this … (more)
This variant disrupts a region of the MEN1 protein in which other variant(s) (p.Glln578*) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This sequence change creates a premature translational stop signal (p.Lys569Aspfs*27) in the MEN1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 42 amino acid(s) of the MEN1 protein. 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. This variant disrupts the NLS2 domain of the MEN1 protein, which is important for DNA binding and repression of cell proliferation (PMID: 15331604, 16449969). While functional studies have not been performed to directly test the effect of this variant on MEN1 protein function, this suggests that disruption of this region of the protein is causative of disease. 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 variant disrupts a region of the MEN1 protein in which other variant(s) (p.Glln578*) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This sequence change creates a premature translational stop signal (p.Lys569Aspfs*27) in the MEN1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 42 amino acid(s) of the MEN1 protein. 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. This variant disrupts the NLS2 domain of the MEN1 protein, which is important for DNA binding and repression of cell proliferation (PMID: 15331604, 16449969). While functional studies have not been performed to directly test the effect of this variant on MEN1 protein function, this suggests that disruption of this region of the protein is causative of disease. For these reasons, this variant has been classified as Pathogenic.
Citations for germline classification of this variant
Help| There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
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.