VCV000134640.27 - ClinVar

NM_001370259.2(MEN1):c.1621A>G (p.Thr541Ala)

Germline

Classification

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.

(10)

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.

Benign

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001370259.2(MEN1):c.1621A>G (p.Thr541Ala)

Variation ID: 134640 Accession: VCV000134640.27

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 11q13.1 11: 64804546 (GRCh38) [ NCBI UCSC ] 11: 64572018 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	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	Jun 9, 2014	Sep 29, 2024	Feb 5, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_001370259.2:c.1621A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001357188.2:p.Thr541Ala	missense
NM_000244.4:c.1636A>G	NP_000235.3:p.Thr546Ala	missense
NM_001370251.2:c.1747A>G	NP_001357180.2:p.Thr583Ala	missense
NM_001370260.2:c.1621A>G	NP_001357189.2:p.Thr541Ala	missense
NM_001370261.2:c.1621A>G	NP_001357190.2:p.Thr541Ala	missense
NM_001370262.2:c.1516A>G	NP_001357191.2:p.Thr506Ala	missense
NM_001370263.2:c.1516A>G	NP_001357192.2:p.Thr506Ala	missense
NM_130799.3:c.1621A>G	NP_570711.2:p.Thr541Ala	missense
NM_130800.3:c.1636A>G	NP_570712.2:p.Thr546Ala	missense
NM_130801.3:c.1636A>G	NP_570713.2:p.Thr546Ala	missense
NM_130802.3:c.1636A>G	NP_570714.2:p.Thr546Ala	missense
NM_130803.3:c.1636A>G	NP_570715.2:p.Thr546Ala	missense
NM_130804.3:c.1636A>G	NP_570716.2:p.Thr546Ala	missense
NC_000011.10:g.64804546T>C
NC_000011.9:g.64572018T>C
NG_008929.1:g.11749=
NG_033040.1:g.3696A>G
LRG_509:g.11749=
LRG_509t2:c.1621=	LRG_509p2:p.Ala541=

... more HGVS ... less HGVS

Protein change

T541A, T506A, T546A, T583A

Other names

Canonical SPDI

NC_000011.10:64804545:T:C

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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.

0.16554 (T)

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD) 0.89377

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.90843

The Genome Aggregation Database (gnomAD), exomes 0.93741

Exome Aggregation Consortium (ExAC) 0.93778

1000 Genomes Project 30x 0.83057

1000 Genomes Project 0.83446

Trans-Omics for Precision Medicine (TOPMed) 0.88099

Links

ClinGen: CA060856 dbSNP: rs2959656 VarSome

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
Gene	OMIM	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.
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.
not specified	Benign (5)	criteria provided, multiple submitters, no conflicts	Jun 22, 2018	RCV000121334.12
Multiple endocrine neoplasia, type 1	Benign (3)	criteria provided, multiple submitters, no conflicts	Feb 5, 2024	RCV000860147.12
not provided	Benign (2)	criteria provided, multiple submitters, no conflicts	Nov 30, 2023	RCV002227065.11

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.
Benign (Mar 23, 2018)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Multiple endocrine neoplasia, type 1 Affected status: unknown Allele origin: germline	Color Diagnostics, LLC DBA Color Health Accession: SCV004359140.1 First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024
Benign (Mar 29, 2016)	criteria provided, single submitter (LMM Criteria) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000539614.1 First in ClinVar: Mar 24, 2015 Last updated: Mar 24, 2015	Comment: Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or … (more) Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency (less) Method: Genome/Exome Filtration
Benign (Jun 22, 2018)	criteria provided, single submitter (EGL ClinVar v180209 classification definitions) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000203003.4 First in ClinVar: Jan 30, 2015 Last updated: Dec 15, 2018	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=MEN1 Number of individuals with the variant: 43 Sex: mixed
Benign (Feb 01, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Multiple endocrine neoplasia, type 1 Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001000095.6 First in ClinVar: Dec 17, 2019 Last updated: Feb 20, 2024
Benign (Nov 30, 2023)	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV002506314.5 First in ClinVar: May 07, 2022 Last updated: Feb 20, 2024
Benign (Feb 05, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Multiple endocrine neoplasia, type 1 (Autosomal dominant inheritance) Affected status: unknown Allele origin: germline	All of Us Research Program, National Institutes of Health Accession: SCV004836523.1 First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024 Comment: This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more) This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)	Number of individuals with the variant: 105503
Benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: not provided	not provided (Autosomal dominant inheritance) Affected status: yes Allele origin: germline	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005319087.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Genome Diagnostics Laboratory, University Medical Center Utrecht Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001978091.1 First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001978533.1 First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021
not provided (Sep 19, 2013)	no classification provided Method: reference population	AllHighlyPenetrant Affected status: unknown Allele origin: germline	ITMI Accession: SCV000085508.1 First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014 Comment: Please see associated publication for description of ethnicities	Publications: PubMed (1) PubMed: 24728327 Observation 1: Ethnicity/Population group: Whole_cohort Observation 2: Ethnicity/Population group: African Observation 3: Ethnicity/Population group: African_European Observation 4: Ethnicity/Population group: Central_Asian Observation 5: Ethnicity/Population group: East_Asian Observation 6: Ethnicity/Population group: European Observation 7: Ethnicity/Population group: Hispanic

Comment:

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency

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:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=MEN1	-	-	-	-

Text-mined citations for rs2959656 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NM_001370259.2(MEN1):c.1621A>G (p.Thr541Ala)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs2959656 ...