NM_001370259.2(MEN1):c.912+1G>C AND Multiple endocrine neoplasia, type 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 15, 2022
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:: RCV000552470.6

Allele description [Variation Report for NM_001370259.2(MEN1):c.912+1G>C]

NM_001370259.2(MEN1):c.912+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.912+1G>C

HGVS:

NC_000011.10:g.64807010C>G
NG_008929.1:g.9285G>C
NG_033040.1:g.1232G>C
NG_033040.2:g.1204G>C
NM_000244.4:c.927+1G>C
NM_001370251.2:c.912+1G>C
NM_001370259.2:c.912+1G>CMANE SELECT
NM_001370260.2:c.912+1G>C
NM_001370261.2:c.912+1G>C
NM_001370262.2:c.807+1G>C
NM_001370263.2:c.807+1G>C
NM_001407142.1:c.912+1G>C
NM_001407143.1:c.912+1G>C
NM_001407144.1:c.912+1G>C
NM_001407145.1:c.927+1G>C
NM_001407146.1:c.912+1G>C
NM_001407147.1:c.912+1G>C
NM_001407148.1:c.807+1G>C
NM_001407149.1:c.807+1G>C
NM_001407150.1:c.927+1G>C
NM_001407151.1:c.807+1G>C
NM_001407152.1:c.912+1G>C
NM_130799.3:c.912+1G>C
NM_130800.3:c.927+1G>C
NM_130801.3:c.927+1G>C
NM_130802.3:c.927+1G>C
NM_130803.3:c.927+1G>C
NM_130804.3:c.927+1G>C
LRG_509t2:c.912+1G>C
LRG_509:g.9285G>C
NC_000011.9:g.64574482C>G
NM_130799.2:c.912+1G>C

Links:

dbSNP: rs398124437

NCBI 1000 Genomes Browser:

rs398124437

Molecular consequence:

NM_000244.4:c.927+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001370251.2:c.912+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001370259.2:c.912+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001370260.2:c.912+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001370261.2:c.912+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001370262.2:c.807+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001370263.2:c.807+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407142.1:c.912+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407143.1:c.912+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407144.1:c.912+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407145.1:c.927+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407146.1:c.912+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407147.1:c.912+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407148.1:c.807+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407149.1:c.807+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407150.1:c.927+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407151.1:c.807+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407152.1:c.912+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_130799.3:c.912+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_130800.3:c.927+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_130801.3:c.927+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_130802.3:c.927+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_130803.3:c.927+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_130804.3:c.927+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]

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
SCV000628108	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 15, 2022)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 10090472, 15714081, 18753104, 16199547, 12112656, 17853334, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000628108

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 15, 2022)

germline

clinical testing

PubMed (7)
[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

Germline mutations in the multiple endocrine neoplasia type 1 gene: evidence for frequent splicing defects.

Mutch MG, Dilley WG, Sanjurjo F, DeBenedetti MK, Doherty GM, Wells SA Jr, Goodfellow PJ, Lairmore TC.

Hum Mutat. 1999;13(3):175-85.

PubMed [citation]

PMID:: 10090472

Clinical testing for multiple endocrine neoplasia type 1 in a DNA diagnostic laboratory.

Klein RD, Salih S, Bessoni J, Bale AE.

Genet Med. 2005 Feb;7(2):131-8.

PubMed [citation]

PMID:: 15714081

See all PubMed Citations (7)

Details of each submission

From Invitae, SCV000628108.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 428012). This variant is also known as IVS6+1G>C. Disruption of this splice site has been observed in individuals with clinical features of multiple endocrine neoplasia type 1 (PMID: 10090472, 15714081, 18753104). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 6 of the MEN1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MEN1 are known to be pathogenic (PMID: 12112656, 17853334).

#	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: Feb 28, 2024

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