NM_001370259.2(MEN1):c.65T>G (p.Leu22Arg) AND Multiple endocrine neoplasia, type 1

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Oct 20, 2020
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:: RCV000018157.10

Allele description [Variation Report for NM_001370259.2(MEN1):c.65T>G (p.Leu22Arg)]

NM_001370259.2(MEN1):c.65T>G (p.Leu22Arg)

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.65T>G (p.Leu22Arg)

Other names:

p.L22R:CTG>CGG

HGVS:

NC_000011.10:g.64810045A>C
NG_008929.1:g.6250T>G
NM_000244.4:c.65T>G
NM_001370251.2:c.65T>G
NM_001370259.2:c.65T>GMANE SELECT
NM_001370260.2:c.65T>G
NM_001370261.2:c.65T>G
NM_001370262.2:c.65T>G
NM_001370263.2:c.65T>G
NM_130799.3:c.65T>G
NM_130800.3:c.65T>G
NM_130801.3:c.65T>G
NM_130802.3:c.65T>G
NM_130803.3:c.65T>G
NM_130804.3:c.65T>G
NP_000235.2:p.Leu22Arg
NP_000235.3:p.Leu22Arg
NP_001357180.2:p.Leu22Arg
NP_001357188.2:p.Leu22Arg
NP_001357189.2:p.Leu22Arg
NP_001357190.2:p.Leu22Arg
NP_001357191.2:p.Leu22Arg
NP_001357192.2:p.Leu22Arg
NP_570711.1:p.Leu22Arg
NP_570711.2:p.Leu22Arg
NP_570712.2:p.Leu22Arg
NP_570713.2:p.Leu22Arg
NP_570714.2:p.Leu22Arg
NP_570715.2:p.Leu22Arg
NP_570716.2:p.Leu22Arg
LRG_509t1:c.65T>G
LRG_509t2:c.65T>G
LRG_509:g.6250T>G
LRG_509p1:p.Leu22Arg
LRG_509p2:p.Leu22Arg
NC_000011.9:g.64577517A>C
NM_000244.3:c.65T>G
NM_130799.2:c.65T>G
O00255:p.Leu22Arg

Protein change:

L22R; LEU22ARG

Links:

UniProtKB: O00255#VAR_005426; OMIM: 613733.0001; dbSNP: rs104894256

NCBI 1000 Genomes Browser:

rs104894256

Molecular consequence:

NM_000244.4:c.65T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001370251.2:c.65T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001370259.2:c.65T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001370260.2:c.65T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001370261.2:c.65T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001370262.2:c.65T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001370263.2:c.65T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_130799.3:c.65T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_130800.3:c.65T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_130801.3:c.65T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_130802.3:c.65T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_130803.3:c.65T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_130804.3:c.65T>G - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000038436	OMIM	no assertion criteria provided	Pathogenic (Apr 18, 1997)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV001406551	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Oct 20, 2020)	germline	clinical testing	PubMed (10) [See all records that cite these PMIDs] 23580576, 22090276, 21819486, 21264250, 20404349, 19749796, 19074834, 9103196, 9498491, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000038436

OMIM

no assertion criteria provided

Pathogenic
(Apr 18, 1997)

germline

literature only

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

SCV001406551

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Oct 20, 2020)

germline

clinical testing

PubMed (10)
[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

Menin epigenetically represses Hedgehog signaling in MEN1 tumor syndrome.

Gurung B, Feng Z, Iwamoto DV, Thiel A, Jin G, Fan CM, Ng JM, Curran T, Hua X.

Cancer Res. 2013 Apr 15;73(8):2650-8. doi: 10.1158/0008-5472.CAN-12-3158. Epub 2013 Apr 11.

PubMed [citation]

PMID:: 23580576
PMCID:: PMC4100916

Menin missense mutants encoded by the MEN1 gene that are targeted to the proteasome: restoration of expression and activity by CHIP siRNA.

Canaff L, Vanbellinghen JF, Kanazawa I, Kwak H, Garfield N, Vautour L, Hendy GN.

J Clin Endocrinol Metab. 2012 Feb;97(2):E282-91. doi: 10.1210/jc.2011-0241. Epub 2011 Nov 16.

PubMed [citation]

PMID:: 22090276

See all PubMed Citations (10)

Details of each submission

From OMIM, SCV000038436.1

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

Description

In a proband with multiple endocrine neoplasia type I (MEN1; 131100), Chandrasekharappa et al. (1997) identified a heterozygous missense mutation in the MEN1 gene, changing residue 22 from leucine to arginine (L22R).

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001406551.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (10)

Description

This sequence change replaces leucine with arginine at codon 22 of the MEN1 protein (p.Leu22Arg). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and arginine. This variant is not present in population databases (ExAC no frequency). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant has been reported to affect MEN1 protein function (PMID: 23580576, 22090276, 21819486, 21264250, 20404349, 19749796, 19074834). This variant has been observed to segregate with clinical features of multiple endocrine neoplasia type 1 in a family (Invitae). In addition, it has been reported in an individual affected with multiple endocrine neoplasia type 1 (PMID: 9103196), and in an individual with a lipoma (PMID: 9498491). ClinVar contains an entry for this variant (Variation ID: 16677).

#	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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