NM_001370259.2(MEN1):c.1387G>T (p.Glu463Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 19, 2021
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:: RCV002396577.2

Allele description [Variation Report for NM_001370259.2(MEN1):c.1387G>T (p.Glu463Ter)]

NM_001370259.2(MEN1):c.1387G>T (p.Glu463Ter)

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.1387G>T (p.Glu463Ter)

HGVS:

NC_000011.10:g.64804780C>A
NG_008929.1:g.11515G>T
NG_033040.2:g.3434G>T
NM_000244.4:c.1402G>T
NM_001370251.2:c.1513G>T
NM_001370259.2:c.1387G>TMANE SELECT
NM_001370260.2:c.1387G>T
NM_001370261.2:c.1387G>T
NM_001370262.2:c.1282G>T
NM_001370263.2:c.1282G>T
NM_001407142.1:c.1513G>T
NM_001407143.1:c.1513G>T
NM_001407144.1:c.1513G>T
NM_001407145.1:c.1402G>T
NM_001407146.1:c.1387G>T
NM_001407147.1:c.1387G>T
NM_001407148.1:c.1282G>T
NM_001407149.1:c.1282G>T
NM_001407150.1:c.1528G>T
NM_001407151.1:c.1408G>T
NM_001407152.1:c.1222G>T
NM_130799.3:c.1387G>T
NM_130800.3:c.1402G>T
NM_130801.3:c.1402G>T
NM_130802.3:c.1402G>T
NM_130803.3:c.1402G>T
NM_130804.3:c.1402G>T
NP_000235.2:p.Glu468Ter
NP_000235.3:p.Glu468Ter
NP_001357180.2:p.Glu505Ter
NP_001357188.2:p.Glu463Ter
NP_001357189.2:p.Glu463Ter
NP_001357190.2:p.Glu463Ter
NP_001357191.2:p.Glu428Ter
NP_001357192.2:p.Glu428Ter
NP_001394071.1:p.Glu505Ter
NP_001394072.1:p.Glu505Ter
NP_001394073.1:p.Glu505Ter
NP_001394074.1:p.Glu468Ter
NP_001394075.1:p.Glu463Ter
NP_001394076.1:p.Glu463Ter
NP_001394077.1:p.Glu428Ter
NP_001394078.1:p.Glu428Ter
NP_001394079.1:p.Glu510Ter
NP_001394080.1:p.Glu470Ter
NP_001394081.1:p.Glu408Ter
NP_570711.1:p.Glu463Ter
NP_570711.2:p.Glu463Ter
NP_570712.2:p.Glu468Ter
NP_570713.2:p.Glu468Ter
NP_570714.2:p.Glu468Ter
NP_570715.2:p.Glu468Ter
NP_570716.2:p.Glu468Ter
LRG_509t1:c.1402G>T
LRG_509t2:c.1387G>T
LRG_509:g.11515G>T
LRG_509p1:p.Glu468Ter
LRG_509p2:p.Glu463Ter
NC_000011.9:g.64572252C>A
NG_033040.1:g.3462G>T
NM_000244.3:c.1402G>T
NM_130799.2:c.1387G>T
NR_176284.1:n.1585G>T
NR_176285.1:n.1597G>T
NR_176286.1:n.1600G>T
NR_176287.1:n.1858G>T

Protein change:

E408*

Molecular consequence:

NM_000244.4:c.1402G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001370251.2:c.1513G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001370259.2:c.1387G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001370260.2:c.1387G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001370261.2:c.1387G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001370262.2:c.1282G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001370263.2:c.1282G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001407142.1:c.1513G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001407143.1:c.1513G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001407144.1:c.1513G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001407145.1:c.1402G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001407146.1:c.1387G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001407147.1:c.1387G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001407148.1:c.1282G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001407149.1:c.1282G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001407150.1:c.1528G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001407151.1:c.1408G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001407152.1:c.1222G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_130799.3:c.1387G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_130800.3:c.1402G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_130801.3:c.1402G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_130802.3:c.1402G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_130803.3:c.1402G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_130804.3:c.1402G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

Recent activity

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growth arrest and DNA damage-inducible protein GADD45 gamma [Homo sapiens]
growth arrest and DNA damage-inducible protein GADD45 gamma [Homo sapiens]
gi|5729836|ref|NP_006696.1|

Protein
Synthetic construct Mus musculus clone IMAGE:100063319, MGC:191063 Rho-associate...
Synthetic construct Mus musculus clone IMAGE:100063319, MGC:191063 Rho-associated coiled-coil containing protein kinase 2 (Rock2) mRNA, encodes complete protein
gi|162318405|gb|BC157053.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002699046	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Aug 19, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 10980535, 23052745 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002699046

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Aug 19, 2021)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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

Mutation analysis of the MEN1 gene in Israeli patients with MEN1 and familial isolated hyperprolactinemia.

Jakobovitz-Picard O, Olchovsky D, Berezin M, Ghodsizade A, Zahavi Z, Karasik A, Rechavi G, Friedman E.

Hum Mutat. 2000 Sep;16(3):269.

PubMed [citation]

PMID:: 10980535

Analysis of genotype-phenotype correlations and survival outcomes in patients with primary hyperparathyroidism caused by multiple endocrine neoplasia type 1: the experience at a single institution.

Horiuchi K, Okamoto T, Iihara M, Tsukada T.

Surg Today. 2013 Aug;43(8):894-9. doi: 10.1007/s00595-012-0354-y. Epub 2012 Oct 9. Erratum in: Surg Today. 2013 Aug;43(8):900.

PubMed [citation]

PMID:: 23052745

Details of each submission

From Ambry Genetics, SCV002699046.2

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

Description

The p.E463* pathogenic mutation (also known as c.1387G>T), located in coding exon 9 of the MEN1 gene, results from a G to T substitution at nucleotide position 1387. This changes the amino acid from a glutamic acid to a stop codon within coding exon 9. This alteration occurs at the 3' terminus of theMEN1 gene, is not expected to trigger nonsense-mediated mRNA decay, and impacts the last 148 amino acids of the protein. However, premature stop codons are typically deleterious in nature and a significant portion of the protein is affected (Ambry internal data). This mutation has been reported in multiple individuals with a clinical diagnosis of multiple endocrine neoplasia type 1 (MEN1) (Jakobovitz-Picard O et al. Hum. Mutat., 2000 Sep;16:269; Horiuchi K et al. Surg Today, 2013 Aug;43:894-9; Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

#	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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