The p.A284V variant (also known as c.851C>T), located in coding exon 5 of the MEN1 gene, results from a C to T substitution at nucleotide position 851. The alanine at codon 284 is replaced by valine, an amino acid with similar properties. This alteration has been observed in multiple individuals with a personal and/or family history that is consistent with MEN1-related disease (Tonelli F et al. Ann Surg, 2006 Jul;244:61-70; Marini F et al. Endocrine, 2018 Oct;62:234-241; Marini F et al. Endocrine, 2018 Oct;62:215-233; Ambry internal data). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
ClinVar Genomic variation as it relates to human health
NM_001370259.2(MEN1):c.851C>T (p.Ala284Val)
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.
Likely 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.851C>T (p.Ala284Val)
Variation ID: 2450220 Accession: VCV002450220.2
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11q13.1 11: 64807072 (GRCh38) [ NCBI UCSC ] 11: 64574544 (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 Apr 15, 2023 May 1, 2024 Dec 22, 2022 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001370259.2:c.851C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001357188.2:p.Ala284Val missense NM_000244.4:c.866C>T NP_000235.3:p.Ala289Val missense NM_001370251.2:c.851C>T NP_001357180.2:p.Ala284Val missense NM_001370260.2:c.851C>T NP_001357189.2:p.Ala284Val missense NM_001370261.2:c.851C>T NP_001357190.2:p.Ala284Val missense NM_001370262.2:c.746C>T NP_001357191.2:p.Ala249Val missense NM_001370263.2:c.746C>T NP_001357192.2:p.Ala249Val missense NM_001407142.1:c.851C>T NP_001394071.1:p.Ala284Val missense NM_001407143.1:c.851C>T NP_001394072.1:p.Ala284Val missense NM_001407144.1:c.851C>T NP_001394073.1:p.Ala284Val missense NM_001407145.1:c.866C>T NP_001394074.1:p.Ala289Val missense NM_001407146.1:c.851C>T NP_001394075.1:p.Ala284Val missense NM_001407147.1:c.851C>T NP_001394076.1:p.Ala284Val missense NM_001407148.1:c.746C>T NP_001394077.1:p.Ala249Val missense NM_001407149.1:c.746C>T NP_001394078.1:p.Ala249Val missense NM_001407150.1:c.866C>T NP_001394079.1:p.Ala289Val missense NM_001407151.1:c.746C>T NP_001394080.1:p.Ala249Val missense NM_001407152.1:c.851C>T NP_001394081.1:p.Ala284Val missense NM_130799.3:c.851C>T NP_570711.2:p.Ala284Val missense NM_130800.3:c.866C>T NP_570712.2:p.Ala289Val missense NM_130801.3:c.866C>T NP_570713.2:p.Ala289Val missense NM_130802.3:c.866C>T NP_570714.2:p.Ala289Val missense NM_130803.3:c.866C>T NP_570715.2:p.Ala289Val missense NM_130804.3:c.866C>T NP_570716.2:p.Ala289Val missense NR_176284.1:n.900C>T non-coding transcript variant NR_176285.1:n.912C>T non-coding transcript variant NR_176286.1:n.915C>T non-coding transcript variant NR_176287.1:n.1173C>T non-coding transcript variant NC_000011.10:g.64807072G>A NC_000011.9:g.64574544G>A NG_008929.1:g.9223C>T NG_033040.1:g.1170C>T NG_033040.2:g.1142C>T LRG_509:g.9223C>T LRG_509t1:c.866C>T LRG_509p1:p.Ala289Val LRG_509t2:c.851C>T LRG_509p2:p.Ala284Val - Protein change
- A249V, A284V, A289V
- Other names
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- Canonical SPDI
- NC_000011.10:64807071:G:A
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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.
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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. |
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| Likely pathogenic (1) |
criteria provided, single submitter
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Dec 22, 2022 | RCV003172098.2 |
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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Likely pathogenic
(Dec 22, 2022)
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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: SCV003860274.2
First in ClinVar: Apr 15, 2023 Last updated: May 01, 2024 |
Comment:
The p.A284V variant (also known as c.851C>T), located in coding exon 5 of the MEN1 gene, results from a C to T substitution at nucleotide … (more)
The p.A284V variant (also known as c.851C>T), located in coding exon 5 of the MEN1 gene, results from a C to T substitution at nucleotide position 851. The alanine at codon 284 is replaced by valine, an amino acid with similar properties. This alteration has been observed in multiple individuals with a personal and/or family history that is consistent with MEN1-related disease (Tonelli F et al. Ann Surg, 2006 Jul;244:61-70; Marini F et al. Endocrine, 2018 Oct;62:234-241; Marini F et al. Endocrine, 2018 Oct;62:215-233; Ambry internal data). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be 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:
The p.A284V variant (also known as c.851C>T), located in coding exon 5 of the MEN1 gene, results from a C to T substitution at nucleotide position 851. The alanine at codon 284 is replaced by valine, an amino acid with similar properties. This alteration has been observed in multiple individuals with a personal and/or family history that is consistent with MEN1-related disease (Tonelli F et al. Ann Surg, 2006 Jul;244:61-70; Marini F et al. Endocrine, 2018 Oct;62:234-241; Marini F et al. Endocrine, 2018 Oct;62:215-233; Ambry internal data). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Correction to: Multiple endocrine neoplasia type 1: analysis of germline MEN1 mutations in the Italian multicenter MEN1 patient database. | Marini F | Endocrine | 2018 | PMID: 30032405 |
| Multiple endocrine neoplasia type 1: analysis of germline MEN1 mutations in the Italian multicenter MEN1 patient database. | Marini F | Endocrine | 2018 | PMID: 29497973 |
| Pancreatectomy in multiple endocrine neoplasia type 1-related gastrinomas and pancreatic endocrine neoplasias. | Tonelli F | Annals of surgery | 2006 | PMID: 16794390 |
Text-mined citations for this variant ...
HelpRecord last updated May 01, 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.