NM_001370259.2(MEN1):c.1328C>A (p.Ser443Tyr) AND Multiple endocrine neoplasia, type 1

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jun 27, 2017
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:: RCV000467767.8

Allele description [Variation Report for NM_001370259.2(MEN1):c.1328C>A (p.Ser443Tyr)]

NM_001370259.2(MEN1):c.1328C>A (p.Ser443Tyr)

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.1328C>A (p.Ser443Tyr)

HGVS:

NC_000011.10:g.64805056G>T
NG_008929.1:g.11239C>A
NG_033040.1:g.3186C>A
NM_000244.4:c.1343C>A
NM_001370251.2:c.1454C>A
NM_001370259.2:c.1328C>AMANE SELECT
NM_001370260.2:c.1328C>A
NM_001370261.2:c.1328C>A
NM_001370262.2:c.1223C>A
NM_001370263.2:c.1223C>A
NM_130799.3:c.1328C>A
NM_130800.3:c.1343C>A
NM_130801.3:c.1343C>A
NM_130802.3:c.1343C>A
NM_130803.3:c.1343C>A
NM_130804.3:c.1343C>A
NP_000235.3:p.Ser448Tyr
NP_001357180.2:p.Ser485Tyr
NP_001357188.2:p.Ser443Tyr
NP_001357189.2:p.Ser443Tyr
NP_001357190.2:p.Ser443Tyr
NP_001357191.2:p.Ser408Tyr
NP_001357192.2:p.Ser408Tyr
NP_570711.1:p.Ser443Tyr
NP_570711.2:p.Ser443Tyr
NP_570712.2:p.Ser448Tyr
NP_570713.2:p.Ser448Tyr
NP_570714.2:p.Ser448Tyr
NP_570715.2:p.Ser448Tyr
NP_570716.2:p.Ser448Tyr
LRG_509t2:c.1328C>A
LRG_509:g.11239C>A
LRG_509p2:p.Ser443Tyr
NC_000011.9:g.64572528G>T
NM_130799.2:c.1328C>A

Protein change:

S408Y

Links:

dbSNP: rs1060499981

NCBI 1000 Genomes Browser:

rs1060499981

Molecular consequence:

NM_000244.4:c.1343C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370251.2:c.1454C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370259.2:c.1328C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370260.2:c.1328C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370261.2:c.1328C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370262.2:c.1223C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370263.2:c.1223C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130799.3:c.1328C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130800.3:c.1343C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130801.3:c.1343C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130802.3:c.1343C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130803.3:c.1343C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130804.3:c.1343C>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

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
SCV000541213	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jun 27, 2017)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 22090276, 17853334, 25309600, 21069576, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000541213

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jun 27, 2017)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

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

Menin missense mutants encoded by the MEN1 gene that are targeted to the proteasome: restoration of expression and activity by CHIP siRNA.

Canaff L, Vanbellinghen JF, Kanazawa I, Kwak H, Garfield N, Vautour L, Hendy GN.

J Clin Endocrinol Metab. 2012 Feb;97(2):E282-91. doi: 10.1210/jc.2011-0241. Epub 2011 Nov 16.

PubMed [citation]

PMID:: 22090276

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.

Schaaf L, Pickel J, Zinner K, Hering U, Höfler M, Goretzki PE, Spelsberg F, Raue F, von zur Mühlen A, Gerl H, Hensen J, Bartsch DK, Rothmund M, Schneyer U, Dralle H, Engelbach M, Karges W, Stalla GK, Höppner W.

Exp Clin Endocrinol Diabetes. 2007 Sep;115(8):509-17.

PubMed [citation]

PMID:: 17853334

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000541213.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

In summary, this variant is a rare missense that has been reported to disrupt protein function and has been reported in affected individuals. This evidence indicates that the variant is pathogenic, but additional data is needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this missense change disrupts protein stability in vitro (PMID: 22090276). This variant has been reported individuals affected with multiple endocrine neoplasia type 1 (MEN1) (PMID: 17853334, 25309600, 21069576). ClinVar contains an entry for this variant (Variation ID: 403825). This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with tyrosine at codon 443 of the MEN1 protein (p.Ser443Tyr). The serine residue is moderately conserved and there is a large physicochemical difference between serine and tyrosine.

#	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