NM_001370259.2(MEN1):c.774G>C (p.Gln258His) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 9, 2016
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:: RCV000034788.2

Allele description [Variation Report for NM_001370259.2(MEN1):c.774G>C (p.Gln258His)]

NM_001370259.2(MEN1):c.774G>C (p.Gln258His)

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.774G>C (p.Gln258His)

HGVS:

NC_000011.10:g.64807561C>G
NG_008929.1:g.8734G>C
NG_033040.1:g.681G>C
NM_000244.4:c.789G>C
NM_001370251.2:c.774G>C
NM_001370259.2:c.774G>CMANE SELECT
NM_001370260.2:c.774G>C
NM_001370261.2:c.774G>C
NM_001370262.2:c.669G>C
NM_001370263.2:c.669G>C
NM_130799.3:c.774G>C
NM_130800.3:c.789G>C
NM_130801.3:c.789G>C
NM_130802.3:c.789G>C
NM_130803.3:c.789G>C
NM_130804.3:c.789G>C
NP_000235.3:p.Gln263His
NP_001357180.2:p.Gln258His
NP_001357188.2:p.Gln258His
NP_001357189.2:p.Gln258His
NP_001357190.2:p.Gln258His
NP_001357191.2:p.Gln223His
NP_001357192.2:p.Gln223His
NP_570711.1:p.Gln258His
NP_570711.2:p.Gln258His
NP_570712.2:p.Gln263His
NP_570713.2:p.Gln263His
NP_570714.2:p.Gln263His
NP_570715.2:p.Gln263His
NP_570716.2:p.Gln263His
LRG_509t2:c.774G>C
LRG_509:g.8734G>C
LRG_509p2:p.Gln258His
NC_000011.9:g.64575033C>G
NM_130799.2:c.774G>C

Protein change:

Q223H

Links:

dbSNP: rs374659656

NCBI 1000 Genomes Browser:

rs374659656

Molecular consequence:

NM_000244.4:c.789G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001370251.2:c.774G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001370259.2:c.774G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001370260.2:c.774G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001370261.2:c.774G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001370262.2:c.669G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001370263.2:c.669G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_130799.3:c.774G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_130800.3:c.789G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_130801.3:c.789G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_130802.3:c.789G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_130803.3:c.789G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_130804.3:c.789G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000043287	Biesecker Lab/Clinical Genomics Section, National Institutes of Health - ClinSeq	no assertion criteria provided	variant of unknown significance (Jul 13, 2012)	germline	research	PubMed (1) [See all records that cite this PMID]
SCV000565127	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (Dec 9, 2016)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000043287

Biesecker Lab/Clinical Genomics Section, National Institutes of Health - ClinSeq

no assertion criteria provided

variant of unknown significance
(Jul 13, 2012)

germline

research

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

SCV000565127

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(Dec 9, 2016)

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	no	1	not provided	not provided	572	not provided	research
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Secondary variants in individuals undergoing exome sequencing: screening of 572 individuals identifies high-penetrance mutations in cancer-susceptibility genes.

Johnston JJ, Rubinstein WS, Facio FM, Ng D, Singh LN, Teer JK, Mullikin JC, Biesecker LG.

Am J Hum Genet. 2012 Jul 13;91(1):97-108. doi: 10.1016/j.ajhg.2012.05.021. Epub 2012 Jun 14.

PubMed [citation]

PMID:: 22703879
PMCID:: PMC3397257

Details of each submission

From Biesecker Lab/Clinical Genomics Section, National Institutes of Health - ClinSeq, SCV000043287.1

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

Description

The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See PubMed ID:22703879 for details.

Description

Converted during submission to Uncertain significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	572	not provided	discovery		1	not provided	not provided	not provided

From GeneDx, SCV000565127.4

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

Description

This variant is denoted MEN1 c.774G>C at the cDNA level, p.Gln258His (Q258H) at the protein level, and results in the change of a Glutamine to a Histidine (CAG>CAC). This variant was observed in 1/572 individuals with atherosclerosis, with no specific information about cancer history (Johnston 2012). MEN1 Gln258His was not observed at a significant allele frequency in the NHLBI Exome Sequencing Project. Since Glutamine and Histidine differ in some properties, this is considered a semi-conservative amino acid substitution. MEN1 Gln258His occurs at a position that is conserved across species and is located in the region of interaction with FANCD2 (UniProt). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether MEN1 Gln258His is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.

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

Last Updated: Sep 29, 2024

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