NM_001370259.2(MEN1):c.1634C>T (p.Pro545Leu) AND Multiple endocrine neoplasia, type 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 11, 2024
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:: RCV001889766.4

Allele description [Variation Report for NM_001370259.2(MEN1):c.1634C>T (p.Pro545Leu)]

NM_001370259.2(MEN1):c.1634C>T (p.Pro545Leu)

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.1634C>T (p.Pro545Leu)

HGVS:

NC_000011.10:g.64804533G>A
NG_008929.1:g.11762C>T
NG_033040.1:g.3709C>T
NM_000244.4:c.1649C>T
NM_001370251.2:c.1760C>T
NM_001370259.2:c.1634C>TMANE SELECT
NM_001370260.2:c.1634C>T
NM_001370261.2:c.1634C>T
NM_001370262.2:c.1529C>T
NM_001370263.2:c.1529C>T
NM_130799.3:c.1634C>T
NM_130800.3:c.1649C>T
NM_130801.3:c.1649C>T
NM_130802.3:c.1649C>T
NM_130803.3:c.1649C>T
NM_130804.3:c.1649C>T
NP_000235.3:p.Pro550Leu
NP_001357180.2:p.Pro587Leu
NP_001357188.2:p.Pro545Leu
NP_001357189.2:p.Pro545Leu
NP_001357190.2:p.Pro545Leu
NP_001357191.2:p.Pro510Leu
NP_001357192.2:p.Pro510Leu
NP_570711.2:p.Pro545Leu
NP_570712.2:p.Pro550Leu
NP_570713.2:p.Pro550Leu
NP_570714.2:p.Pro550Leu
NP_570715.2:p.Pro550Leu
NP_570716.2:p.Pro550Leu
LRG_509t2:c.1634C>T
LRG_509:g.11762C>T
NC_000011.9:g.64572005G>A
NM_130799.2:c.1634C>T

Protein change:

P510L

Links:

dbSNP: rs1592630610

NCBI 1000 Genomes Browser:

rs1592630610

Molecular consequence:

NM_000244.4:c.1649C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001370251.2:c.1760C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001370259.2:c.1634C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001370260.2:c.1634C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001370261.2:c.1634C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001370262.2:c.1529C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001370263.2:c.1529C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_130799.3:c.1634C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_130800.3:c.1649C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_130801.3:c.1649C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_130802.3:c.1649C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_130803.3:c.1649C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_130804.3:c.1649C>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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002143652	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 11, 2024)	germline	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

SCV002143652

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 11, 2024)

germline

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	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

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002143652.3

#	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 proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 545 of the MEN1 protein (p.Pro545Leu). This variant is not present in population databases (gnomAD no frequency). 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: 1376890). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MEN1 protein function. 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

Last Updated: Sep 29, 2024

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