The c.1694dupT pathogenic mutation, located in coding exon 9 of the MEN1 gene, results from a duplication of T at nucleotide position 1694, causing a translational frameshift with a predicted alternate stop codon (p.V566Gfs*31). This alteration occurs at the 3' terminus of theMEN1 gene, is not expected to trigger nonsense-mediated mRNA decay, and impacts the last 45 amino acids of the protein. However, premature stop codons are typically deleterious in nature and a significant portion of the protein is affected and the impacted region is critical for protein function (Ambry internal data). This variant has been observed in at least one individual with a personal and/or family history that is consistent with MEN1-associated disease (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.
ClinVar Genomic variation as it relates to human health
NM_001370259.2(MEN1):c.1694dup (p.Val566fs)
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.1694dup (p.Val566fs)
Variation ID: 3229077 Accession: VCV003229077.1
- Type and length
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Duplication, 1 bp
- Location
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Cytogenetic: 11q13.1 11: 64804472-64804473 (GRCh38) [ NCBI UCSC ] 11: 64571944-64571945 (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 1, 2024 May 1, 2024 Mar 11, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001370259.2:c.1694dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001357188.2:p.Val566fs frameshift NM_000244.4:c.1709dup NP_000235.3:p.Val571fs frameshift NM_001370251.2:c.1820dup NP_001357180.2:p.Val608fs frameshift NM_001370260.2:c.1694dup NP_001357189.2:p.Val566fs frameshift NM_001370261.2:c.1694dup NP_001357190.2:p.Val566fs frameshift NM_001370262.2:c.1589dup NP_001357191.2:p.Val531fs frameshift NM_001370263.2:c.1589dup NP_001357192.2:p.Val531fs frameshift NM_001407142.1:c.1820dup NP_001394071.1:p.Val608fs frameshift NM_001407143.1:c.1820dup NP_001394072.1:p.Val608fs frameshift NM_001407144.1:c.1820dup NP_001394073.1:p.Val608fs frameshift NM_001407145.1:c.1709dup NP_001394074.1:p.Val571fs frameshift NM_001407146.1:c.1694dup NP_001394075.1:p.Val566fs frameshift NM_001407147.1:c.1694dup NP_001394076.1:p.Val566fs frameshift NM_001407148.1:c.1589dup NP_001394077.1:p.Val531fs frameshift NM_001407149.1:c.1589dup NP_001394078.1:p.Val531fs frameshift NM_001407150.1:c.1835dup NP_001394079.1:p.Val613fs frameshift NM_001407151.1:c.1715dup NP_001394080.1:p.Val573fs frameshift NM_001407152.1:c.1529dup NP_001394081.1:p.Val511fs frameshift NM_130799.2:c.1694dupT frameshift NM_130799.3:c.1694dup NP_570711.2:p.Val566fs frameshift NM_130800.3:c.1709dup NP_570712.2:p.Val571fs frameshift NM_130801.3:c.1709dup NP_570713.2:p.Val571fs frameshift NM_130802.3:c.1709dup NP_570714.2:p.Val571fs frameshift NM_130803.3:c.1709dup NP_570715.2:p.Val571fs frameshift NM_130804.3:c.1709dup NP_570716.2:p.Val571fs frameshift NR_176284.1:n.1892dup non-coding transcript variant NR_176285.1:n.1904dup non-coding transcript variant NR_176286.1:n.1907dup non-coding transcript variant NR_176287.1:n.2165dup non-coding transcript variant NC_000011.10:g.64804473dup NC_000011.9:g.64571945dup NG_008929.1:g.11822dup NG_033040.1:g.3769dup NG_033040.2:g.3741dup LRG_509:g.11822dup LRG_509t1:c.1709dup LRG_509p1:p.Val571Glyfs LRG_509t2:c.1694dup LRG_509p2:p.Val566Glyfs - Protein change
- V511fs, V531fs, V566fs, V571fs, V573fs, V608fs, V613fs
- Other names
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- Canonical SPDI
- NC_000011.10:64804472:A:AA
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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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Mar 11, 2024 | RCV004522700.1 |
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
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
(Mar 11, 2024)
|
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: SCV005030384.1
First in ClinVar: May 01, 2024 Last updated: May 01, 2024 |
Comment:
The c.1694dupT pathogenic mutation, located in coding exon 9 of the MEN1 gene, results from a duplication of T at nucleotide position 1694, causing a … (more)
The c.1694dupT pathogenic mutation, located in coding exon 9 of the MEN1 gene, results from a duplication of T at nucleotide position 1694, causing a translational frameshift with a predicted alternate stop codon (p.V566Gfs*31). This alteration occurs at the 3' terminus of theMEN1 gene, is not expected to trigger nonsense-mediated mRNA decay, and impacts the last 45 amino acids of the protein. However, premature stop codons are typically deleterious in nature and a significant portion of the protein is affected and the impacted region is critical for protein function (Ambry internal data). This variant has been observed in at least one individual with a personal and/or family history that is consistent with MEN1-associated disease (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)
|
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:
The c.1694dupT pathogenic mutation, located in coding exon 9 of the MEN1 gene, results from a duplication of T at nucleotide position 1694, causing a translational frameshift with a predicted alternate stop codon (p.V566Gfs*31). This alteration occurs at the 3' terminus of theMEN1 gene, is not expected to trigger nonsense-mediated mRNA decay, and impacts the last 45 amino acids of the protein. However, premature stop codons are typically deleterious in nature and a significant portion of the protein is affected and the impacted region is critical for protein function (Ambry internal data). This variant has been observed in at least one individual with a personal and/or family history that is consistent with MEN1-associated disease (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.
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 May 08, 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.