Variant summary: MEN1 c.796delC (p.Leu266CysfsX15) 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. The variant was absent in 250288 control chromosomes (gnomAD). To our knowledge, no occurrence of c.796delC in individuals affected with Multiple Endocrine Neoplasia Type 1 and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as pathogenic.
ClinVar Genomic variation as it relates to human health
NM_001370259.2(MEN1):c.796del (p.Leu266fs)
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.
(2)
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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
2
criteria provided, multiple submitters, no conflicts
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.796del (p.Leu266fs)
Variation ID: 3063935 Accession: VCV003063935.2
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 11q13.1 11: 64807207 (GRCh38) [ NCBI UCSC ] 11: 64574679 (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 Mar 30, 2024 May 1, 2024 Feb 29, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001370259.2:c.796del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001357188.2:p.Leu266fs frameshift NM_000244.4:c.811del NP_000235.3:p.Leu271fs frameshift NM_001370251.2:c.796del NP_001357180.2:p.Leu266fs frameshift NM_001370260.2:c.796del NP_001357189.2:p.Leu266fs frameshift NM_001370261.2:c.796del NP_001357190.2:p.Leu266fs frameshift NM_001370262.2:c.691del NP_001357191.2:p.Leu231fs frameshift NM_001370263.2:c.691del NP_001357192.2:p.Leu231fs frameshift NM_001407142.1:c.796del NP_001394071.1:p.Leu266fs frameshift NM_001407143.1:c.796del NP_001394072.1:p.Leu266fs frameshift NM_001407144.1:c.796del NP_001394073.1:p.Leu266fs frameshift NM_001407145.1:c.811del NP_001394074.1:p.Leu271fs frameshift NM_001407146.1:c.796del NP_001394075.1:p.Leu266fs frameshift NM_001407147.1:c.796del NP_001394076.1:p.Leu266fs frameshift NM_001407148.1:c.691del NP_001394077.1:p.Leu231fs frameshift NM_001407149.1:c.691del NP_001394078.1:p.Leu231fs frameshift NM_001407150.1:c.811del NP_001394079.1:p.Leu271fs frameshift NM_001407151.1:c.691del NP_001394080.1:p.Leu231fs frameshift NM_001407152.1:c.796del NP_001394081.1:p.Leu266fs frameshift NM_130799.3:c.796del NP_570711.2:p.Leu266fs frameshift NM_130799.3:c.796delC frameshift NM_130800.3:c.811del NP_570712.2:p.Leu271fs frameshift NM_130801.3:c.811del NP_570713.2:p.Leu271fs frameshift NM_130802.3:c.811del NP_570714.2:p.Leu271fs frameshift NM_130803.3:c.811del NP_570715.2:p.Leu271fs frameshift NM_130804.3:c.811del NP_570716.2:p.Leu271fs frameshift NR_176284.1:n.845del non-coding transcript variant NR_176285.1:n.857del non-coding transcript variant NR_176286.1:n.860del non-coding transcript variant NR_176287.1:n.1118del non-coding transcript variant NC_000011.10:g.64807207del NC_000011.9:g.64574679del NG_008929.1:g.9088del NG_033040.1:g.1035del NG_033040.2:g.1007del LRG_509:g.9088del LRG_509t1:c.811del LRG_509p1:p.Leu271Cysfs LRG_509t2:c.796del LRG_509p2:p.Leu266Cysfs - Protein change
- L231fs, L266fs, L271fs
- Other names
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- Canonical SPDI
- NC_000011.10:64807206: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 | ||
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| 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 (2) |
criteria provided, multiple submitters, no conflicts
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Feb 29, 2024 | RCV003988523.2 |
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
(Jan 15, 2024)
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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: SCV004803429.1
First in ClinVar: Mar 30, 2024 Last updated: Mar 30, 2024 |
Comment:
Variant summary: MEN1 c.796delC (p.Leu266CysfsX15) 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.796delC (p.Leu266CysfsX15) 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. The variant was absent in 250288 control chromosomes (gnomAD). To our knowledge, no occurrence of c.796delC in individuals affected with Multiple Endocrine Neoplasia Type 1 and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Feb 29, 2024)
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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:
unknown
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Myriad Genetics, Inc.
Accession: SCV004930950.1
First in ClinVar: May 01, 2024 Last updated: May 01, 2024 |
Comment:
This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
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Comment:
Comment:
This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
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:
Variant summary: MEN1 c.796delC (p.Leu266CysfsX15) 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. The variant was absent in 250288 control chromosomes (gnomAD). To our knowledge, no occurrence of c.796delC in individuals affected with Multiple Endocrine Neoplasia Type 1 and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as pathogenic.
Comment:
This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
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.