NM_001370259.2(MEN1):c.770TGCAGC[3] (p.257LQ[3]) AND Multiple endocrine neoplasia, type 1

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Oct 3, 2023
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:: RCV000632129.15

Allele description [Variation Report for NM_001370259.2(MEN1):c.770TGCAGC[3] (p.257LQ[3])]

NM_001370259.2(MEN1):c.770TGCAGC[3] (p.257LQ[3])

Gene:

MEN1:menin 1 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

11q13.1

Genomic location:

Preferred name:

NM_001370259.2(MEN1):c.770TGCAGC[3] (p.257LQ[3])

HGVS:

NC_000011.10:g.64807555CTGCAG[3]
NG_008929.1:g.8730TGCAGC[3]
NG_008929.1:g.8736_8741dup
NG_033040.1:g.677TGCAGC[3]
NM_000244.4:c.785TGCAGC[3]
NM_001370251.2:c.770TGCAGC[3]
NM_001370259.2:c.770TGCAGC[3]MANE SELECT
NM_001370260.2:c.770TGCAGC[3]
NM_001370261.2:c.770TGCAGC[3]
NM_001370262.2:c.665TGCAGC[3]
NM_001370263.2:c.665TGCAGC[3]
NM_130799.3:c.770TGCAGC[3]
NM_130800.3:c.785TGCAGC[3]
NM_130801.3:c.785TGCAGC[3]
NM_130802.3:c.785TGCAGC[3]
NM_130803.3:c.785TGCAGC[3]
NM_130804.3:c.785TGCAGC[3]
NP_000235.3:p.262LQ[3]
NP_001357180.2:p.257LQ[3]
NP_001357188.2:p.257LQ[3]
NP_001357189.2:p.257LQ[3]
NP_001357190.2:p.257LQ[3]
NP_001357191.2:p.222LQ[3]
NP_001357192.2:p.222LQ[3]
NP_570711.2:p.257LQ[3]
NP_570712.2:p.262LQ[3]
NP_570713.2:p.262LQ[3]
NP_570714.2:p.262LQ[3]
NP_570715.2:p.262LQ[3]
NP_570716.2:p.262LQ[3]
LRG_509:g.8736_8741dup
NC_000011.9:g.64575025_64575026insGCTGCA
NC_000011.9:g.64575027CTGCAG[3]
NG_008929.1:g.8736_8741dup
NM_130799.2:c.776_781dup

Links:

OMIM: 613733.0030; dbSNP: rs1555165485

NCBI 1000 Genomes Browser:

rs1555165485

Molecular consequence:

NM_000244.4:c.785TGCAGC[3] - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_001370251.2:c.770TGCAGC[3] - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_001370259.2:c.770TGCAGC[3] - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_001370260.2:c.770TGCAGC[3] - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_001370261.2:c.770TGCAGC[3] - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_001370262.2:c.665TGCAGC[3] - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_001370263.2:c.665TGCAGC[3] - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_130799.3:c.770TGCAGC[3] - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_130800.3:c.785TGCAGC[3] - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_130801.3:c.785TGCAGC[3] - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_130802.3:c.785TGCAGC[3] - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_130803.3:c.785TGCAGC[3] - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_130804.3:c.785TGCAGC[3] - inframe_insertion - [Sequence Ontology: SO:0001821]

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
SCV000038465	OMIM	no assertion criteria provided	Pathogenic (Sep 1, 2002)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000753233	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 3, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 12417605, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000038465

OMIM

no assertion criteria provided

Pathogenic
(Sep 1, 2002)

germline

literature only

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

SCV000753233

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 3, 2023)

germline

clinical testing

PubMed (2)
[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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A novel six-nucleotide insertion in exon 4 of the MEN1 gene, 878insCTGCAG, in three patients with familial insulinoma and primary hyperparathyroidism.

Okamoto H, Tamada A, Hai N, Doi M, Uchimura I, Hirata Y, Kosugi S.

Jpn J Clin Oncol. 2002 Sep;32(9):368-70.

PubMed [citation]

PMID:: 12417605

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From OMIM, SCV000038465.1

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

Description

In 3 members of a Japanese family with MEN1 (131100) and a predisposition to insulinoma, Okamoto et al. (2002) identified a heterozygous germline mutation in exon 4 of the MEN1 gene, 878insCTGCAG (insertion of 6 nucleotides after nucleotide 878), resulting in the insertion of 2 amino acids, leu-gln, after amino acid 256 of the menin protein (256insLQ). The authors noted that CTGCAG is a palindromic sequence, repeated twice in the wildtype allele from nucleotides 879 to 890. Okamoto et al. (2002) found a significant difference (p = 0.0022) on chi square analysis of 72 MEN1 patients with or without germline mutations in exon 4 and with or without insulinomas, and suggested that there may be a correlation between insulinoma development and mutations in exon 4 where JunD binding occurs.

#	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, SCV000753233.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant, c.776_781dup, results in the insertion of 2 amino acid(s) of the MEN1 protein (p.Leu259_Gln260dup), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with clinical features of multiple endocrine neoplasia type 1 (PMID: 12417605; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 527275). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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

Last Updated: Apr 20, 2024

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