NM_001370259.2(MEN1):c.1393_1396del (p.Ala465fs) AND Multiple endocrine neoplasia, type 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 27, 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:: RCV003062402.3

Allele description [Variation Report for NM_001370259.2(MEN1):c.1393_1396del (p.Ala465fs)]

NM_001370259.2(MEN1):c.1393_1396del (p.Ala465fs)

Gene:

MEN1:menin 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

11q13.1

Genomic location:

Preferred name:

NM_001370259.2(MEN1):c.1393_1396del (p.Ala465fs)

HGVS:

NC_000011.10:g.64804773_64804776del
NG_008929.1:g.11521_11524del
NG_033040.2:g.3440_3443del
NM_000244.4:c.1408_1411del
NM_001370251.2:c.1519_1522del
NM_001370259.2:c.1393_1396delMANE SELECT
NM_001370260.2:c.1393_1396del
NM_001370261.2:c.1393_1396del
NM_001370262.2:c.1288_1291del
NM_001370263.2:c.1288_1291del
NM_001407142.1:c.1517_1520delCGGC
NM_001407143.1:c.1517_1520delCGGC
NM_001407144.1:c.1517_1520delCGGC
NM_001407145.1:c.1406_1409delCGGC
NM_001407146.1:c.1391_1394delCGGC
NM_001407147.1:c.1391_1394delCGGC
NM_001407148.1:c.1286_1289delCGGC
NM_001407149.1:c.1286_1289delCGGC
NM_001407150.1:c.1532_1535delCGGC
NM_001407151.1:c.1412_1415delCGGC
NM_001407152.1:c.1226_1229delCGGC
NM_130799.3:c.1393_1396del
NM_130800.3:c.1408_1411del
NM_130801.3:c.1408_1411del
NM_130802.3:c.1408_1411del
NM_130803.3:c.1408_1411del
NM_130804.3:c.1408_1411del
NP_000235.2:p.Ala470Argfs
NP_000235.3:p.Ala470fs
NP_001357180.2:p.Ala507fs
NP_001357188.2:p.Ala465fs
NP_001357189.2:p.Ala465fs
NP_001357190.2:p.Ala465fs
NP_001357191.2:p.Ala430fs
NP_001357192.2:p.Ala430fs
NP_001394071.1:p.Ala507Argfs
NP_001394072.1:p.Ala507Argfs
NP_001394073.1:p.Ala507Argfs
NP_001394074.1:p.Ala470Argfs
NP_001394075.1:p.Ala465Argfs
NP_001394076.1:p.Ala465Argfs
NP_001394077.1:p.Ala430Argfs
NP_001394078.1:p.Ala430Argfs
NP_001394079.1:p.Ala512Argfs
NP_001394080.1:p.Ala472Argfs
NP_001394081.1:p.Ala410Argfs
NP_570711.1:p.Ala465Argfs
NP_570711.2:p.Ala465fs
NP_570712.2:p.Ala470fs
NP_570713.2:p.Ala470fs
NP_570714.2:p.Ala470fs
NP_570715.2:p.Ala470fs
NP_570716.2:p.Ala470fs
LRG_509t1:c.1406_1409del
LRG_509t2:c.1391_1394del
LRG_509:g.11521_11524del
LRG_509p1:p.Ala470Argfs
LRG_509p2:p.Ala465Argfs
NC_000011.9:g.64572243_64572246del
NC_000011.9:g.64572245_64572248del
NG_033040.1:g.3468_3471del
NM_000244.3:c.1406_1409delCGGC
NM_130799.2:c.1391_1394delCGGC
NR_176284.1:n.1589_1592delCGGC
NR_176285.1:n.1601_1604delCGGC
NR_176286.1:n.1604_1607delCGGC
NR_176287.1:n.1862_1865delCGGC

Protein change:

A430fs

Molecular consequence:

NM_000244.4:c.1408_1411del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370251.2:c.1519_1522del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370259.2:c.1393_1396del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370260.2:c.1393_1396del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370261.2:c.1393_1396del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370262.2:c.1288_1291del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370263.2:c.1288_1291del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407142.1:c.1517_1520delCGGC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407143.1:c.1517_1520delCGGC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407144.1:c.1517_1520delCGGC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407145.1:c.1406_1409delCGGC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407146.1:c.1391_1394delCGGC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407147.1:c.1391_1394delCGGC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407148.1:c.1286_1289delCGGC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407149.1:c.1286_1289delCGGC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407150.1:c.1532_1535delCGGC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407151.1:c.1412_1415delCGGC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407152.1:c.1226_1229delCGGC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_130799.3:c.1393_1396del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_130800.3:c.1408_1411del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_130801.3:c.1408_1411del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_130802.3:c.1408_1411del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_130803.3:c.1408_1411del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_130804.3:c.1408_1411del - frameshift variant - [Sequence Ontology: SO:0001589]

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

Recent activity

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Homo sapiens protein phosphatase 6 regulatory subunit 3 (PPP6R3), transcript var...
Homo sapiens protein phosphatase 6 regulatory subunit 3 (PPP6R3), transcript variant 6, mRNA
gi|1677500144|ref|NM_001164161.2|

Nucleotide
NADH dehydrogenase subunit 4 (mitochondrion) [Fulmarus glacialis]
NADH dehydrogenase subunit 4 (mitochondrion) [Fulmarus glacialis]
gi|1910804042|gb|QOD97295.1|

Protein
Beta-mannosidase, partial [Fulmarus glacialis]
Beta-mannosidase, partial [Fulmarus glacialis]
gi|679005311|gb|KFW06347.1||gnl|WGS |N327_07728

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003439819	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 27, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 15331604, 16449969, 10090472, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003439819

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 27, 2022)

germline

clinical testing

PubMed (4)
[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

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 (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003439819.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

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). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant is also known as 1392-1395delGGCC. This premature translational stop signal has been observed in individual(s) with multiple endocrine neoplasia type 1 (PMID: 10090472). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ala465Argfs*93) in the MEN1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 146 amino acid(s) of the MEN1 protein.

#	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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