NM_001370259.2(MEN1):c.1350G>C (p.Gln450His) AND Multiple endocrine neoplasia, type 1

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Aug 17, 2023
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:: RCV001350334.5

Allele description [Variation Report for NM_001370259.2(MEN1):c.1350G>C (p.Gln450His)]

NM_001370259.2(MEN1):c.1350G>C (p.Gln450His)

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.1350G>C (p.Gln450His)

HGVS:

NC_000011.10:g.64805034C>G
NG_008929.1:g.11261G>C
NG_033040.1:g.3208G>C
NM_000244.4:c.1365G>C
NM_001370251.2:c.1476G>C
NM_001370259.2:c.1350G>CMANE SELECT
NM_001370260.2:c.1350G>C
NM_001370261.2:c.1350G>C
NM_001370262.2:c.1245G>C
NM_001370263.2:c.1245G>C
NM_130799.3:c.1350G>C
NM_130800.3:c.1365G>C
NM_130801.3:c.1365G>C
NM_130802.3:c.1365G>C
NM_130803.3:c.1365G>C
NM_130804.3:c.1365G>C
NP_000235.3:p.Gln455His
NP_001357180.2:p.Gln492His
NP_001357188.2:p.Gln450His
NP_001357189.2:p.Gln450His
NP_001357190.2:p.Gln450His
NP_001357191.2:p.Gln415His
NP_001357192.2:p.Gln415His
NP_570711.1:p.Gln450His
NP_570711.2:p.Gln450His
NP_570712.2:p.Gln455His
NP_570713.2:p.Gln455His
NP_570714.2:p.Gln455His
NP_570715.2:p.Gln455His
NP_570716.2:p.Gln455His
LRG_509t2:c.1350G>C
LRG_509:g.11261G>C
LRG_509p2:p.Gln450His
NC_000011.9:g.64572506C>G
NM_130799.2:c.1350G>C

Protein change:

Q415H

Links:

dbSNP: rs1592636161

NCBI 1000 Genomes Browser:

rs1592636161

Molecular consequence:

NM_000244.4:c.1365G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001370251.2:c.1476G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001370259.2:c.1350G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001370260.2:c.1350G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001370261.2:c.1350G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001370262.2:c.1245G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001370263.2:c.1245G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_130799.3:c.1350G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_130800.3:c.1365G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_130801.3:c.1365G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_130802.3:c.1365G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_130803.3:c.1365G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_130804.3:c.1365G>C - 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
SCV001544725	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Aug 17, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 17576681, 9536098, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001544725

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Aug 17, 2023)

germline

clinical testing

PubMed (3)
[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

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]

PMID:: 17576681
PMCID:: PMC1934990

Statistical features of human exons and their flanking regions.

Zhang MQ.

Hum Mol Genet. 1998 May;7(5):919-32.

PubMed [citation]

PMID:: 9536098

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001544725.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This sequence change affects codon 450 of the MEN1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the MEN1 protein. This variant also falls at the last nucleotide of exon 9, which is part of the consensus splice site for this exon. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with MEN1-related tumors (Invitae). ClinVar contains an entry for this variant (Variation ID: 818932). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#	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

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