NM_001370259.2(MEN1):c.1351-1G>C AND Multiple endocrine neoplasia, type 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 15, 2019
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000540660.7

Allele description [Variation Report for NM_001370259.2(MEN1):c.1351-1G>C]

NM_001370259.2(MEN1):c.1351-1G>C

Gene:

MEN1:menin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q13.1

Genomic location:

Preferred name:

NM_001370259.2(MEN1):c.1351-1G>C

HGVS:

NC_000011.10:g.64804817C>G
NG_008929.1:g.11478G>C
NG_033040.1:g.3425G>C
NG_033040.2:g.3397G>C
NM_000244.4:c.1366-1G>C
NM_001370251.2:c.1477-1G>C
NM_001370259.2:c.1351-1G>CMANE SELECT
NM_001370260.2:c.1351-1G>C
NM_001370261.2:c.1351-1G>C
NM_001370262.2:c.1246-1G>C
NM_001370263.2:c.1246-1G>C
NM_001407142.1:c.1477-1G>C
NM_001407143.1:c.1477-1G>C
NM_001407144.1:c.1477-1G>C
NM_001407145.1:c.1366-1G>C
NM_001407146.1:c.1351-1G>C
NM_001407147.1:c.1351-1G>C
NM_001407148.1:c.1246-1G>C
NM_001407149.1:c.1246-1G>C
NM_001407150.1:c.1492-1G>C
NM_001407151.1:c.1372-1G>C
NM_001407152.1:c.1186-1G>C
NM_130799.3:c.1351-1G>C
NM_130800.3:c.1366-1G>C
NM_130801.3:c.1366-1G>C
NM_130802.3:c.1366-1G>C
NM_130803.3:c.1366-1G>C
NM_130804.3:c.1366-1G>C
LRG_509t2:c.1351-1G>C
LRG_509:g.11478G>C
NC_000011.9:g.64572289C>G
NM_130799.2:c.1351-1G>C

Links:

dbSNP: rs794728629

NCBI 1000 Genomes Browser:

rs794728629

Molecular consequence:

NM_000244.4:c.1366-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001370251.2:c.1477-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001370259.2:c.1351-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001370260.2:c.1351-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001370261.2:c.1351-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001370262.2:c.1246-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001370263.2:c.1246-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407142.1:c.1477-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407143.1:c.1477-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407144.1:c.1477-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407145.1:c.1366-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407146.1:c.1351-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407147.1:c.1351-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407148.1:c.1246-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407149.1:c.1246-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407150.1:c.1492-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407151.1:c.1372-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407152.1:c.1186-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_130799.3:c.1351-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_130800.3:c.1366-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_130801.3:c.1366-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_130802.3:c.1366-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_130803.3:c.1366-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_130804.3:c.1366-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]

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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Escherichia coli KTE28 genomic scaffold acEnN-supercont1.2, whole genome shotgun...
Escherichia coli KTE28 genomic scaffold acEnN-supercont1.2, whole genome shotgun sequence
gi|475999052|gnl|WGS:ANSY01|acEnN-s ont1.2|gb|KB732346.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000628038	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 15, 2019)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 10617276, 17576681, 9536098, 17185897, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000628038

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 15, 2019)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Molecular pathology of multiple endocrine neoplasia type I: two novel germline mutations and updated classification of mutations affecting MEN1 gene.

Martín-Campos JM, Catasús L, Chico A, Mayoral C, Lagarda E, Gallart L, Mato E, Rodríguez-Espinosa J, Matías-Guiu X, De Leiva A, Blanco-Vaca F.

Diagn Mol Pathol. 1999 Dec;8(4):195-204.

PubMed [citation]

PMID:: 10617276

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]

PMID:: 17576681
PMCID:: PMC1934990

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000628038.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. This sequence change affects an acceptor splice site in the last intron (intron 9) of the MEN1 gene. While this is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is not present in population databases (ExAC no frequency). Disruption of this splice site has been observed in individuals affected with clinical features of multiple endocrine neoplasia type 1 (PMID: 10617276, Invitae). ClinVar contains an entry for this variant (Variation ID: 200985). Disruption of this splice site has been reported to affect MEN1 protein function (PMID: 17185897). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that disruption of this splice site disrupts mRNA splicing (PMID: 17185897).

#	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

Last Updated: Sep 29, 2024

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