NM_001370259.2(MEN1):c.1281T>A (p.Ser427Arg) AND Multiple endocrine neoplasia, type 1

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Nov 12, 2018
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:: RCV001002226.8

Allele description [Variation Report for NM_001370259.2(MEN1):c.1281T>A (p.Ser427Arg)]

NM_001370259.2(MEN1):c.1281T>A (p.Ser427Arg)

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.1281T>A (p.Ser427Arg)

HGVS:

NC_000011.10:g.64805103A>T
NG_008929.1:g.11192T>A
NG_033040.1:g.3139T>A
NM_000244.4:c.1296T>A
NM_001370251.2:c.1407T>A
NM_001370259.2:c.1281T>AMANE SELECT
NM_001370260.2:c.1281T>A
NM_001370261.2:c.1281T>A
NM_001370262.2:c.1176T>A
NM_001370263.2:c.1176T>A
NM_130799.3:c.1281T>A
NM_130800.3:c.1296T>A
NM_130801.3:c.1296T>A
NM_130802.3:c.1296T>A
NM_130803.3:c.1296T>A
NM_130804.3:c.1296T>A
NP_000235.3:p.Ser432Arg
NP_001357180.2:p.Ser469Arg
NP_001357188.2:p.Ser427Arg
NP_001357189.2:p.Ser427Arg
NP_001357190.2:p.Ser427Arg
NP_001357191.2:p.Ser392Arg
NP_001357192.2:p.Ser392Arg
NP_570711.1:p.Ser427Arg
NP_570711.2:p.Ser427Arg
NP_570712.2:p.Ser432Arg
NP_570713.2:p.Ser432Arg
NP_570714.2:p.Ser432Arg
NP_570715.2:p.Ser432Arg
NP_570716.2:p.Ser432Arg
LRG_509t2:c.1281T>A
LRG_509:g.11192T>A
LRG_509p2:p.Ser427Arg
NC_000011.9:g.64572575A>T
NM_130799.2:c.1281T>A

Protein change:

S392R

Links:

dbSNP: rs1114167528

NCBI 1000 Genomes Browser:

rs1114167528

Molecular consequence:

NM_000244.4:c.1296T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370251.2:c.1407T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370259.2:c.1281T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370260.2:c.1281T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370261.2:c.1281T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370262.2:c.1176T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370263.2:c.1176T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130799.3:c.1281T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130800.3:c.1296T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130801.3:c.1296T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130802.3:c.1296T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130803.3:c.1296T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130804.3:c.1296T>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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001160100	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process)	Likely pathogenic (Nov 12, 2018)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001160100

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process)

Likely pathogenic
(Nov 12, 2018)

germline

clinical testing

Citation Link

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

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV001160100.1

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

Description

The MEN1 c.1281T>A; p.Ser427Arg variant is reported in the literature in multiple individuals affected with multiple endocrine neoplasia type 1 (Kouvaraki 2002, Ambry Genetics). This variant is reported in ClinVar (Variation ID: 428072), and is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. The serine at codon 427 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Additionally, other variants at this codon (c.1279A>C, p.Ser427Arg; c.1280G>T, p.Ser427Ile) have been reported in individuals with multiple endocrine neoplasia type 1 (Schaaf 2007, Ambry Genetics). Based on available information, the c.1281T>A; p.Ser427Arg variant is considered to be likely pathogenic. References: Kouvaraki MA et al. Genotype-phenotype analysis in multiple endocrine neoplasia type 1. Arch Surg. 2002 Jun;137(6):641-7. Schaaf L et al. Developing effective screening strategies in multiple endocrine neoplasia type 1 (MEN 1) on the basis of clinical and sequencing data of German patients with MEN 1. Exp Clin Endocrinol Diabetes. 2007 Sep;115(8):509-17.

#	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: May 1, 2024

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