NM_001370259.2(MEN1):c.1270dup (p.Glu424fs) AND Multiple endocrine neoplasia, type 1

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 28, 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:: RCV004018363.2

Allele description [Variation Report for NM_001370259.2(MEN1):c.1270dup (p.Glu424fs)]

NM_001370259.2(MEN1):c.1270dup (p.Glu424fs)

Gene:

MEN1:menin 1 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

11q13.1

Genomic location:

Preferred name:

NM_001370259.2(MEN1):c.1270dup (p.Glu424fs)

HGVS:

NC_000011.10:g.64805116dup
NG_008929.1:g.11181dup
NG_033040.1:g.3128dup
NG_033040.2:g.3100dup
NM_000244.4:c.1285dup
NM_001370251.2:c.1396dup
NM_001370259.2:c.1270dupMANE SELECT
NM_001370260.2:c.1270dup
NM_001370261.2:c.1270dup
NM_001370262.2:c.1165dup
NM_001370263.2:c.1165dup
NM_001407142.1:c.1396dup
NM_001407143.1:c.1396dup
NM_001407144.1:c.1396dup
NM_001407145.1:c.1285dup
NM_001407146.1:c.1270dup
NM_001407147.1:c.1270dup
NM_001407148.1:c.1165dup
NM_001407149.1:c.1165dup
NM_001407150.1:c.1411dup
NM_001407151.1:c.1291dup
NM_001407152.1:c.1186-298dup
NM_130799.3:c.1270dup
NM_130800.3:c.1285dup
NM_130801.3:c.1285dup
NM_130802.3:c.1285dup
NM_130803.3:c.1285dup
NM_130804.3:c.1285dup
NP_000235.2:p.Glu429Glyfs
NP_000235.3:p.Glu429fs
NP_001357180.2:p.Glu466fs
NP_001357188.2:p.Glu424fs
NP_001357189.2:p.Glu424fs
NP_001357190.2:p.Glu424fs
NP_001357191.2:p.Glu389fs
NP_001357192.2:p.Glu389fs
NP_001394071.1:p.Glu466fs
NP_001394072.1:p.Glu466fs
NP_001394073.1:p.Glu466fs
NP_001394074.1:p.Glu429fs
NP_001394075.1:p.Glu424fs
NP_001394076.1:p.Glu424fs
NP_001394077.1:p.Glu389fs
NP_001394078.1:p.Glu389fs
NP_001394079.1:p.Glu471fs
NP_001394080.1:p.Glu431fs
NP_570711.1:p.Glu424Glyfs
NP_570711.2:p.Glu424fs
NP_570712.2:p.Glu429fs
NP_570713.2:p.Glu429fs
NP_570714.2:p.Glu429fs
NP_570715.2:p.Glu429fs
NP_570716.2:p.Glu429fs
LRG_509t1:c.1283dup
LRG_509t2:c.1268dup
LRG_509:g.11181dup
LRG_509p1:p.Glu429Glyfs
LRG_509p2:p.Glu424Glyfs
NC_000011.10:g.64805113_64805114insC
NC_000011.9:g.64572588dup
NM_000244.3:c.1283dup
NM_130799.2:c.1268dup
NR_176284.1:n.1468dup
NR_176285.1:n.1480dup
NR_176286.1:n.1483dup
NR_176287.1:n.1741dup

Protein change:

E389fs

Molecular consequence:

NM_000244.4:c.1285dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370251.2:c.1396dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370259.2:c.1270dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370260.2:c.1270dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370261.2:c.1270dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370262.2:c.1165dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370263.2:c.1165dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407142.1:c.1396dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407143.1:c.1396dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407144.1:c.1396dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407145.1:c.1285dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407146.1:c.1270dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407147.1:c.1270dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407148.1:c.1165dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407149.1:c.1165dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407150.1:c.1411dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407151.1:c.1291dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_130799.3:c.1270dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_130800.3:c.1285dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_130801.3:c.1285dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_130802.3:c.1285dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_130803.3:c.1285dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_130804.3:c.1285dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407152.1:c.1186-298dup - intron variant - [Sequence Ontology: SO:0001627]
NR_176284.1:n.1468dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176285.1:n.1480dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176286.1:n.1483dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176287.1:n.1741dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV004848111	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely Pathogenic (Jan 28, 2019)	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

SCV004848111

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely Pathogenic
(Jan 28, 2019)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV004848111.1

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

Description

The p.Glu429fs variant in MEN1 has not been previously reported in individuals with multiple endocrine neoplasia type 1 and was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 429 and leads to a premature termination codon 25 amino acids downstream. This alteration removes the nuclear localization signals and is predicted to lead to an absent protein or a truncated protein that is unable to translocate to the nucleus, with consequent loss of menin functionality. Heterozygous loss of function of function of the MEN1 gene is an established disease mechanism in multiple endocrine neoplasia type 1. In summary, although additional studies are required to fully establish its clinical significance, the p.Glu429fs variant is likely 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: Jun 23, 2024

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