NM_001370259.2(MEN1):c.343C>G (p.Arg115Gly) AND Multiple endocrine neoplasia, type 1

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Oct 13, 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:: RCV000709161.10

Allele description [Variation Report for NM_001370259.2(MEN1):c.343C>G (p.Arg115Gly)]

NM_001370259.2(MEN1):c.343C>G (p.Arg115Gly)

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.343C>G (p.Arg115Gly)

HGVS:

NC_000011.10:g.64809767G>C
NG_008929.1:g.6528C>G
NM_000244.4:c.343C>G
NM_001370251.2:c.343C>G
NM_001370259.2:c.343C>GMANE SELECT
NM_001370260.2:c.343C>G
NM_001370261.2:c.343C>G
NM_001370262.2:c.343C>G
NM_001370263.2:c.343C>G
NM_130799.3:c.343C>G
NM_130800.3:c.343C>G
NM_130801.3:c.343C>G
NM_130802.3:c.343C>G
NM_130803.3:c.343C>G
NM_130804.3:c.343C>G
NP_000235.3:p.Arg115Gly
NP_001357180.2:p.Arg115Gly
NP_001357188.2:p.Arg115Gly
NP_001357189.2:p.Arg115Gly
NP_001357190.2:p.Arg115Gly
NP_001357191.2:p.Arg115Gly
NP_001357192.2:p.Arg115Gly
NP_570711.1:p.Arg115Gly
NP_570711.2:p.Arg115Gly
NP_570712.2:p.Arg115Gly
NP_570713.2:p.Arg115Gly
NP_570714.2:p.Arg115Gly
NP_570715.2:p.Arg115Gly
NP_570716.2:p.Arg115Gly
LRG_509t2:c.343C>G
LRG_509:g.6528C>G
LRG_509p2:p.Arg115Gly
NC_000011.9:g.64577239G>C
NM_130799.2:c.343C>G

Protein change:

R115G

Links:

dbSNP: rs1565651402

NCBI 1000 Genomes Browser:

rs1565651402

Molecular consequence:

NM_000244.4:c.343C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001370251.2:c.343C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001370259.2:c.343C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001370260.2:c.343C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001370261.2:c.343C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001370262.2:c.343C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001370263.2:c.343C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_130799.3:c.343C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_130800.3:c.343C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_130801.3:c.343C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_130802.3:c.343C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_130803.3:c.343C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_130804.3:c.343C>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
SCV000838460	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Uncertain significance (Jul 2, 2018)	unknown	clinical testing	Citation Link,
SCV000962724	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 13, 2023)	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

SCV000838460

Mendelics

criteria provided, single submitter

(Mendelics Assertion Criteria 2017)

Uncertain significance
(Jul 2, 2018)

unknown

clinical testing

Citation Link,

SCV000962724

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 13, 2023)

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
not provided	unknown	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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Mendelics, SCV000838460.2

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

#	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

From Invitae, SCV000962724.6

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

Description

This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 115 of the MEN1 protein (p.Arg115Gly). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MEN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 584772). 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) performed at Invitae indicates that this missense variant is expected to disrupt MEN1 protein function. 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.

#	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: Feb 28, 2024

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