NM_001370259.2(MEN1):c.1344G>C (p.Glu448Asp) AND Multiple endocrine neoplasia, type 1

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Mar 5, 2024
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:: RCV001984224.7

Allele description [Variation Report for NM_001370259.2(MEN1):c.1344G>C (p.Glu448Asp)]

NM_001370259.2(MEN1):c.1344G>C (p.Glu448Asp)

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.1344G>C (p.Glu448Asp)

HGVS:

NC_000011.10:g.64805040C>G
NG_008929.1:g.11255G>C
NG_033040.1:g.3202G>C
NM_000244.4:c.1359G>C
NM_001370251.2:c.1470G>C
NM_001370259.2:c.1344G>CMANE SELECT
NM_001370260.2:c.1344G>C
NM_001370261.2:c.1344G>C
NM_001370262.2:c.1239G>C
NM_001370263.2:c.1239G>C
NM_130799.3:c.1344G>C
NM_130800.3:c.1359G>C
NM_130801.3:c.1359G>C
NM_130802.3:c.1359G>C
NM_130803.3:c.1359G>C
NM_130804.3:c.1359G>C
NP_000235.3:p.Glu453Asp
NP_001357180.2:p.Glu490Asp
NP_001357188.2:p.Glu448Asp
NP_001357189.2:p.Glu448Asp
NP_001357190.2:p.Glu448Asp
NP_001357191.2:p.Glu413Asp
NP_001357192.2:p.Glu413Asp
NP_570711.2:p.Glu448Asp
NP_570712.2:p.Glu453Asp
NP_570713.2:p.Glu453Asp
NP_570714.2:p.Glu453Asp
NP_570715.2:p.Glu453Asp
NP_570716.2:p.Glu453Asp
LRG_509:g.11255G>C
NC_000011.9:g.64572512C>G

Protein change:

E413D

Links:

dbSNP: rs371339952

NCBI 1000 Genomes Browser:

rs371339952

Molecular consequence:

NM_000244.4:c.1359G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001370251.2:c.1470G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001370259.2:c.1344G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001370260.2:c.1344G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001370261.2:c.1344G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001370262.2:c.1239G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001370263.2:c.1239G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_130799.3:c.1344G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_130800.3:c.1359G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_130801.3:c.1359G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_130802.3:c.1359G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_130803.3:c.1359G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_130804.3:c.1359G>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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
SCV002279816	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 21, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005427761	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Mar 5, 2024)	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

SCV002279816

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 21, 2021)

germline

clinical testing

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

SCV005427761

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(Mar 5, 2024)

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	1	not provided	not provided	143475	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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002279816.3

#	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) performed at Invitae indicates that this missense variant is not expected to disrupt MEN1 protein function. This variant has not been reported in the literature in individuals with MEN1-related conditions. This variant is present in population databases (rs371339952, ExAC 0.002%). This sequence change replaces glutamic acid with aspartic acid at codon 448 of the MEN1 protein (p.Glu448Asp). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and aspartic acid.

#	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

From All of Us Research Program, National Institutes of Health, SCV005427761.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	143475	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Dec 22, 2024

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