NM_001370259.2(MEN1):c.1451G>A (p.Arg484Gln) AND Multiple endocrine neoplasia, type 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 20, 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:: RCV003095182.3

Allele description [Variation Report for NM_001370259.2(MEN1):c.1451G>A (p.Arg484Gln)]

NM_001370259.2(MEN1):c.1451G>A (p.Arg484Gln)

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.1451G>A (p.Arg484Gln)

HGVS:

NC_000011.10:g.64804716C>T
NG_008929.1:g.11579G>A
NG_033040.2:g.3498G>A
NM_000244.4:c.1466G>A
NM_001370251.2:c.1577G>A
NM_001370259.2:c.1451G>AMANE SELECT
NM_001370260.2:c.1451G>A
NM_001370261.2:c.1451G>A
NM_001370262.2:c.1346G>A
NM_001370263.2:c.1346G>A
NM_001407142.1:c.1577G>A
NM_001407143.1:c.1577G>A
NM_001407144.1:c.1577G>A
NM_001407145.1:c.1466G>A
NM_001407146.1:c.1451G>A
NM_001407147.1:c.1451G>A
NM_001407148.1:c.1346G>A
NM_001407149.1:c.1346G>A
NM_001407150.1:c.1592G>A
NM_001407151.1:c.1472G>A
NM_001407152.1:c.1286G>A
NM_130799.3:c.1451G>A
NM_130800.3:c.1466G>A
NM_130801.3:c.1466G>A
NM_130802.3:c.1466G>A
NM_130803.3:c.1466G>A
NM_130804.3:c.1466G>A
NP_000235.2:p.Arg489Gln
NP_000235.3:p.Arg489Gln
NP_001357180.2:p.Arg526Gln
NP_001357188.2:p.Arg484Gln
NP_001357189.2:p.Arg484Gln
NP_001357190.2:p.Arg484Gln
NP_001357191.2:p.Arg449Gln
NP_001357192.2:p.Arg449Gln
NP_001394071.1:p.Arg526Gln
NP_001394072.1:p.Arg526Gln
NP_001394073.1:p.Arg526Gln
NP_001394074.1:p.Arg489Gln
NP_001394075.1:p.Arg484Gln
NP_001394076.1:p.Arg484Gln
NP_001394077.1:p.Arg449Gln
NP_001394078.1:p.Arg449Gln
NP_001394079.1:p.Arg531Gln
NP_001394080.1:p.Arg491Gln
NP_001394081.1:p.Arg429Gln
NP_570711.1:p.Arg484Gln
NP_570711.2:p.Arg484Gln
NP_570712.2:p.Arg489Gln
NP_570713.2:p.Arg489Gln
NP_570714.2:p.Arg489Gln
NP_570715.2:p.Arg489Gln
NP_570716.2:p.Arg489Gln
LRG_509t1:c.1466G>A
LRG_509t2:c.1451G>A
LRG_509:g.11579G>A
LRG_509p1:p.Arg489Gln
LRG_509p2:p.Arg484Gln
NC_000011.9:g.64572188C>T
NG_033040.1:g.3526G>A
NM_000244.3:c.1466G>A
NM_130799.2:c.1451G>A
NR_176284.1:n.1649G>A
NR_176285.1:n.1661G>A
NR_176286.1:n.1664G>A
NR_176287.1:n.1922G>A

Protein change:

R429Q

Molecular consequence:

NM_000244.4:c.1466G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370251.2:c.1577G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370259.2:c.1451G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370260.2:c.1451G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370261.2:c.1451G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370262.2:c.1346G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370263.2:c.1346G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407142.1:c.1577G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407143.1:c.1577G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407144.1:c.1577G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407145.1:c.1466G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407146.1:c.1451G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407147.1:c.1451G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407148.1:c.1346G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407149.1:c.1346G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407150.1:c.1592G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407151.1:c.1472G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407152.1:c.1286G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130799.3:c.1451G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130800.3:c.1466G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130801.3:c.1466G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130802.3:c.1466G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130803.3:c.1466G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130804.3:c.1466G>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

NRPB (0)
Protein Family Models

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
SCV003510394	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 20, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003510394

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 20, 2022)

germline

clinical testing

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

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003510394.2

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MEN1 protein function. ClinVar contains an entry for this variant (Variation ID: 1772963). 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 replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 484 of the MEN1 protein (p.Arg484Gln).

#	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