NM_001370259.2(MEN1):c.1456G>T (p.Glu486Ter) AND Multiple endocrine neoplasia, type 1

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Oct 19, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001381741.6

Allele description [Variation Report for NM_001370259.2(MEN1):c.1456G>T (p.Glu486Ter)]

NM_001370259.2(MEN1):c.1456G>T (p.Glu486Ter)

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.1456G>T (p.Glu486Ter)

HGVS:

NC_000011.10:g.64804711C>A
NG_008929.1:g.11584G>T
NG_033040.1:g.3531G>T
NM_000244.4:c.1471G>T
NM_001370251.2:c.1582G>T
NM_001370259.2:c.1456G>TMANE SELECT
NM_001370260.2:c.1456G>T
NM_001370261.2:c.1456G>T
NM_001370262.2:c.1351G>T
NM_001370263.2:c.1351G>T
NM_130799.3:c.1456G>T
NM_130800.3:c.1471G>T
NM_130801.3:c.1471G>T
NM_130802.3:c.1471G>T
NM_130803.3:c.1471G>T
NM_130804.3:c.1471G>T
NP_000235.3:p.Glu491Ter
NP_001357180.2:p.Glu528Ter
NP_001357188.2:p.Glu486Ter
NP_001357189.2:p.Glu486Ter
NP_001357190.2:p.Glu486Ter
NP_001357191.2:p.Glu451Ter
NP_001357192.2:p.Glu451Ter
NP_570711.2:p.Glu486Ter
NP_570712.2:p.Glu491Ter
NP_570713.2:p.Glu491Ter
NP_570714.2:p.Glu491Ter
NP_570715.2:p.Glu491Ter
NP_570716.2:p.Glu491Ter
LRG_509:g.11584G>T
NC_000011.9:g.64572183C>A

Protein change:

E451*

Links:

dbSNP: rs2136089217

NCBI 1000 Genomes Browser:

rs2136089217

Molecular consequence:

NM_000244.4:c.1471G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001370251.2:c.1582G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001370259.2:c.1456G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001370260.2:c.1456G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001370261.2:c.1456G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001370262.2:c.1351G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001370263.2:c.1351G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_130799.3:c.1456G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_130800.3:c.1471G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_130801.3:c.1471G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_130802.3:c.1471G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_130803.3:c.1471G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_130804.3:c.1471G>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV001580239	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 30, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 15331604, 16449969, 28492532
SCV004185971	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Pathogenic (Oct 19, 2023)	unknown	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001580239

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 30, 2022)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV004185971

Myriad Genetics, Inc.

criteria provided, single submitter

(Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))

Pathogenic
(Oct 19, 2023)

unknown

clinical testing

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

Citations

PubMed

Direct binding of DNA by tumor suppressor menin.

La P, Silva AC, Hou Z, Wang H, Schnepp RW, Yan N, Shi Y, Hua X.

J Biol Chem. 2004 Nov 19;279(47):49045-54. Epub 2004 Aug 24.

PubMed [citation]

PMID:: 15331604
PMCID:: PMC2858586

Tumor suppressor menin: the essential role of nuclear localization signal domains in coordinating gene expression.

La P, Desmond A, Hou Z, Silva AC, Schnepp RW, Hua X.

Oncogene. 2006 Jun 15;25(25):3537-46. Epub 2006 Jan 30.

PubMed [citation]

PMID:: 16449969

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001580239.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant has not been reported in the literature in individuals affected with MEN1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu486*) in the MEN1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 125 amino acid(s) of the MEN1 protein. ClinVar contains an entry for this variant (Variation ID: 1069776). For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the MEN1 protein in which other variant(s) (p.Thr580Argfs*8) have been determined to be pathogenic (PMID: 15331604, 16449969; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site.

#	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

From Myriad Genetics, Inc., SCV004185971.1

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

Description

This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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