NM_001370259.2(MEN1):c.710C>T (p.Ala237Val) AND Multiple endocrine neoplasia, type 1

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 27, 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:: RCV000465273.11

Allele description [Variation Report for NM_001370259.2(MEN1):c.710C>T (p.Ala237Val)]

NM_001370259.2(MEN1):c.710C>T (p.Ala237Val)

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.710C>T (p.Ala237Val)

HGVS:

NC_000011.10:g.64807625G>A
NG_008929.1:g.8670C>T
NG_033040.1:g.617C>T
NM_000244.4:c.725C>T
NM_001370251.2:c.710C>T
NM_001370259.2:c.710C>TMANE SELECT
NM_001370260.2:c.710C>T
NM_001370261.2:c.710C>T
NM_001370262.2:c.605C>T
NM_001370263.2:c.605C>T
NM_130799.3:c.710C>T
NM_130800.3:c.725C>T
NM_130801.3:c.725C>T
NM_130802.3:c.725C>T
NM_130803.3:c.725C>T
NM_130804.3:c.725C>T
NP_000235.3:p.Ala242Val
NP_001357180.2:p.Ala237Val
NP_001357188.2:p.Ala237Val
NP_001357189.2:p.Ala237Val
NP_001357190.2:p.Ala237Val
NP_001357191.2:p.Ala202Val
NP_001357192.2:p.Ala202Val
NP_570711.1:p.Ala237Val
NP_570711.2:p.Ala237Val
NP_570712.2:p.Ala242Val
NP_570713.2:p.Ala242Val
NP_570714.2:p.Ala242Val
NP_570715.2:p.Ala242Val
NP_570716.2:p.Ala242Val
LRG_509t2:c.710C>T
LRG_509:g.8670C>T
LRG_509p2:p.Ala237Val
NC_000011.9:g.64575097G>A
NM_130799.2:c.710C>T

Protein change:

A202V

Links:

dbSNP: rs760289964

NCBI 1000 Genomes Browser:

rs760289964

Molecular consequence:

NM_000244.4:c.725C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001370251.2:c.710C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001370259.2:c.710C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001370260.2:c.710C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001370261.2:c.710C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001370262.2:c.605C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001370263.2:c.605C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_130799.3:c.710C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_130800.3:c.725C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_130801.3:c.725C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_130802.3:c.725C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_130803.3:c.725C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_130804.3:c.725C>T - 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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Mus musculus telomerase associated protein 1, mRNA (cDNA clone MGC:91078 IMAGE:3...
Mus musculus telomerase associated protein 1, mRNA (cDNA clone MGC:91078 IMAGE:30457924), complete cds
gi|52789435|gb|BC082996.1|

Nucleotide
Chain B, TFIID TBP ASSOCIATED FACTOR 62
Chain B, TFIID TBP ASSOCIATED FACTOR 62
gi|1942937|pdb|1TAF|B

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000541181	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 27, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004194424	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Oct 26, 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

SCV000541181

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 27, 2023)

germline

clinical testing

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

SCV004194424

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Oct 26, 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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	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, SCV000541181.10

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

Description

This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 237 of the MEN1 protein (p.Ala237Val). This variant is present in population databases (rs760289964, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with MEN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 403803). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MEN1 protein function with a positive predictive value of 95%. 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.

#	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, SCV004194424.1

#	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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