NM_001370259.2(MEN1):c.628_631del (p.Thr210fs) AND Multiple endocrine neoplasia, type 1

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jan 18, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000018163.16

Allele description [Variation Report for NM_001370259.2(MEN1):c.628_631del (p.Thr210fs)]

NM_001370259.2(MEN1):c.628_631del (p.Thr210fs)

Gene:

MEN1:menin 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

11q13.1

Genomic location:

Preferred name:

NM_001370259.2(MEN1):c.628_631del (p.Thr210fs)

HGVS:

NC_000011.10:g.64807917_64807920del
NG_008929.1:g.8378_8381del
NG_033040.1:g.325_328del
NM_000244.4:c.643_646del
NM_001370251.2:c.628_631del
NM_001370259.2:c.628_631delMANE SELECT
NM_001370260.2:c.628_631del
NM_001370261.2:c.628_631del
NM_001370262.2:c.549+79_549+82del
NM_001370263.2:c.549+79_549+82del
NM_130799.3:c.628_631del
NM_130800.3:c.643_646del
NM_130801.3:c.643_646del
NM_130802.3:c.643_646del
NM_130803.3:c.643_646del
NM_130804.3:c.643_646del
NP_000235.3:p.Thr215fs
NP_001357180.2:p.Thr210fs
NP_001357188.2:p.Thr210fs
NP_001357189.2:p.Thr210fs
NP_001357190.2:p.Thr210fs
NP_570711.2:p.Thr210fs
NP_570712.2:p.Thr215fs
NP_570713.2:p.Thr215fs
NP_570714.2:p.Thr215fs
NP_570715.2:p.Thr215fs
NP_570716.2:p.Thr215fs
LRG_509:g.8378_8381del
NC_000011.9:g.64575386_64575389del
NC_000011.9:g.64575389_64575392del
NM_130799.2:c.628_631delACAG
p.T210SfsX13

Protein change:

T210fs

Links:

OMIM: 613733.0007; dbSNP: rs794728640

NCBI 1000 Genomes Browser:

rs794728640

Molecular consequence:

NM_000244.4:c.643_646del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370251.2:c.628_631del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370259.2:c.628_631del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370260.2:c.628_631del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370261.2:c.628_631del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_130799.3:c.628_631del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_130800.3:c.643_646del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_130801.3:c.643_646del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_130802.3:c.643_646del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_130803.3:c.643_646del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_130804.3:c.643_646del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370262.2:c.549+79_549+82del - intron variant - [Sequence Ontology: SO:0001627]
NM_001370263.2:c.549+79_549+82del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Multiple endocrine neoplasia, type 1 (MEN1)
Synonyms:: MEA I; MEN I; Endocrine adenomatosis multiple; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007540; MeSH: D018761; MedGen: C0025267; Orphanet: 652; OMIM: 131100

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000038442	OMIM	no assertion criteria provided	Pathogenic (Apr 18, 1997)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000541231	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 18, 2024)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 12112656, 17853334, 9709921, 10664520, 17879353, 22026581, 23154721, 25309785, 28492532
SCV000595774	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 30, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000038442

OMIM

no assertion criteria provided

Pathogenic
(Apr 18, 1997)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

SCV000541231

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 18, 2024)

germline

clinical testing

PubMed (9)
[See all records that cite these PMIDs]

SCV000595774

Genetic Services Laboratory, University of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Nov 30, 2016)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Positional cloning of the gene for multiple endocrine neoplasia-type 1.

Chandrasekharappa SC, Guru SC, Manickam P, Olufemi SE, Collins FS, Emmert-Buck MR, Debelenko LV, Zhuang Z, Lubensky IA, Liotta LA, Crabtree JS, Wang Y, Roe BA, Weisemann J, Boguski MS, Agarwal SK, Kester MB, Kim YS, Heppner C, Dong Q, Spiegel AM, Burns AL, et al.

Science. 1997 Apr 18;276(5311):404-7.

PubMed [citation]

PMID:: 9103196

Germline mutation profile of MEN1 in multiple endocrine neoplasia type 1: search for correlation between phenotype and the functional domains of the MEN1 protein.

Wautot V, Vercherat C, Lespinasse J, Chambe B, Lenoir GM, Zhang CX, Porchet N, Cordier M, Béroud C, Calender A.

Hum Mutat. 2002 Jul;20(1):35-47.

PubMed [citation]

PMID:: 12112656

See all PubMed Citations (11)

Details of each submission

From OMIM, SCV000038442.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a proband with MEN1 (131100), Chandrasekharappa et al. (1997) identified a heterozygous deletion of 4 bp in the MEN1 gene, starting from nucleotide position 735.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV000541231.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

This sequence change creates a premature translational stop signal (p.Thr210Serfs*13) in the MEN1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MEN1 are known to be pathogenic (PMID: 12112656, 17853334). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with multiple endocrine neoplasia type 1 (PMID: 9709921, 10664520, 17879353, 22026581, 23154721, 25309785). ClinVar contains an entry for this variant (Variation ID: 200997). For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genetic Services Laboratory, University of Chicago, SCV000595774.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 1, 2024

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