NM_001370259.2(MEN1):c.824G>A (p.Arg275Lys) AND Multiple endocrine neoplasia, type 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 26, 2023
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:: RCV000820746.10

Allele description [Variation Report for NM_001370259.2(MEN1):c.824G>A (p.Arg275Lys)]

NM_001370259.2(MEN1):c.824G>A (p.Arg275Lys)

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.824G>A (p.Arg275Lys)

HGVS:

NC_000011.10:g.64807179C>T
NG_008929.1:g.9116G>A
NG_033040.1:g.1063G>A
NM_000244.4:c.839G>A
NM_001370251.2:c.824G>A
NM_001370259.2:c.824G>AMANE SELECT
NM_001370260.2:c.824G>A
NM_001370261.2:c.824G>A
NM_001370262.2:c.719G>A
NM_001370263.2:c.719G>A
NM_130799.3:c.824G>A
NM_130800.3:c.839G>A
NM_130801.3:c.839G>A
NM_130802.3:c.839G>A
NM_130803.3:c.839G>A
NM_130804.3:c.839G>A
NP_000235.3:p.Arg280Lys
NP_001357180.2:p.Arg275Lys
NP_001357188.2:p.Arg275Lys
NP_001357189.2:p.Arg275Lys
NP_001357190.2:p.Arg275Lys
NP_001357191.2:p.Arg240Lys
NP_001357192.2:p.Arg240Lys
NP_570711.1:p.Arg275Lys
NP_570711.2:p.Arg275Lys
NP_570712.2:p.Arg280Lys
NP_570713.2:p.Arg280Lys
NP_570714.2:p.Arg280Lys
NP_570715.2:p.Arg280Lys
NP_570716.2:p.Arg280Lys
LRG_509t2:c.824G>A
LRG_509:g.9116G>A
LRG_509p2:p.Arg275Lys
NC_000011.9:g.64574651C>T
NM_130799.2:c.824G>A

Protein change:

R240K

Links:

dbSNP: rs1187634059

NCBI 1000 Genomes Browser:

rs1187634059

Molecular consequence:

NM_000244.4:c.839G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370251.2:c.824G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370259.2:c.824G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370260.2:c.824G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370261.2:c.824G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370262.2:c.719G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370263.2:c.719G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130799.3:c.824G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130800.3:c.839G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130801.3:c.839G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130802.3:c.839G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130803.3:c.839G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130804.3:c.839G>A - 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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000961472	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 26, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 23778871, 28298337, 17576681, 9536098, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000961472

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 26, 2023)

germline

clinical testing

PubMed (5)
[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

A MEN1 syndrome with a paraganglioma.

Jamilloux Y, Favier J, Pertuit M, Delage-Corre M, Lopez S, Teissier MP, Mathonnet M, Galinat S, Barlier A, Archambeaud F.

Eur J Hum Genet. 2014 Feb;22(2):283-5. doi: 10.1038/ejhg.2013.128. Epub 2013 Jun 19.

PubMed [citation]

PMID:: 23778871
PMCID:: PMC3895646

Radiological surveillance in multiple endocrine neoplasia type 1: a double-edged sword?

Casey RT, Saunders D, Challis BG, Pitfield D, Cheow H, Shaw A, Simpson HL.

Endocr Connect. 2017 Apr;6(3):151-158. doi: 10.1530/EC-17-0006. Epub 2017 Mar 15.

PubMed [citation]

PMID:: 28298337
PMCID:: PMC5424776

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000961472.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

ClinVar contains an entry for this variant (Variation ID: 662978). This missense change has been observed in individuals with multiple endocrine neoplasia type 1 (PMID: 23778871, 28298337). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 275 of the MEN1 protein (p.Arg275Lys). This variant also falls at the last nucleotide of exon 5, which is part of the consensus splice site for this exon. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as 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: Sep 29, 2024

ClinVar

Relating variation to medicine