NM_001370259.2(MEN1):c.1387G>A (p.Glu463Lys) AND Multiple endocrine neoplasia, type 1

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jul 16, 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:: RCV001222478.8

Allele description [Variation Report for NM_001370259.2(MEN1):c.1387G>A (p.Glu463Lys)]

NM_001370259.2(MEN1):c.1387G>A (p.Glu463Lys)

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.1387G>A (p.Glu463Lys)

HGVS:

NC_000011.10:g.64804780C>T
NG_008929.1:g.11515G>A
NG_033040.1:g.3462G>A
NM_000244.4:c.1402G>A
NM_001370251.2:c.1513G>A
NM_001370259.2:c.1387G>AMANE SELECT
NM_001370260.2:c.1387G>A
NM_001370261.2:c.1387G>A
NM_001370262.2:c.1282G>A
NM_001370263.2:c.1282G>A
NM_130799.3:c.1387G>A
NM_130800.3:c.1402G>A
NM_130801.3:c.1402G>A
NM_130802.3:c.1402G>A
NM_130803.3:c.1402G>A
NM_130804.3:c.1402G>A
NP_000235.3:p.Glu468Lys
NP_001357180.2:p.Glu505Lys
NP_001357188.2:p.Glu463Lys
NP_001357189.2:p.Glu463Lys
NP_001357190.2:p.Glu463Lys
NP_001357191.2:p.Glu428Lys
NP_001357192.2:p.Glu428Lys
NP_570711.1:p.Glu463Lys
NP_570711.2:p.Glu463Lys
NP_570712.2:p.Glu468Lys
NP_570713.2:p.Glu468Lys
NP_570714.2:p.Glu468Lys
NP_570715.2:p.Glu468Lys
NP_570716.2:p.Glu468Lys
LRG_509t2:c.1387G>A
LRG_509:g.11515G>A
LRG_509p2:p.Glu463Lys
NC_000011.9:g.64572252C>T
NM_130799.2:c.1387G>A

Protein change:

E428K

Links:

dbSNP: rs748102589

NCBI 1000 Genomes Browser:

rs748102589

Molecular consequence:

NM_000244.4:c.1402G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370251.2:c.1513G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370259.2:c.1387G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370260.2:c.1387G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370261.2:c.1387G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370262.2:c.1282G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370263.2:c.1282G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130799.3:c.1387G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130800.3:c.1402G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130801.3:c.1402G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130802.3:c.1402G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130803.3:c.1402G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130804.3:c.1402G>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

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E2 ubiquitin-conjugating protein RAD6 [Saccharomyces cerevisiae S288C]
E2 ubiquitin-conjugating protein RAD6 [Saccharomyces cerevisiae S288C]
gi|6321380|ref|NP_011457.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001394577	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 24, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004194472	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jul 16, 2023)	unknown	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

SCV001394577

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 24, 2020)

germline

clinical testing

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

SCV004194472

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jul 16, 2023)

unknown

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. 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, SCV001394577.5

#	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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with MEN1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with lysine at codon 463 of the MEN1 protein (p.Glu463Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine.

#	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 Baylor Genetics, SCV004194472.1

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

Last Updated: Sep 29, 2024

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