NM_001370259.2(MEN1):c.530T>G (p.Leu177Arg) AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Mar 3, 2021
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:: RCV002344651.2

Allele description [Variation Report for NM_001370259.2(MEN1):c.530T>G (p.Leu177Arg)]

NM_001370259.2(MEN1):c.530T>G (p.Leu177Arg)

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.530T>G (p.Leu177Arg)

HGVS:

NC_000011.10:g.64808015A>C
NG_008929.1:g.8280T>G
NG_033040.2:g.199T>G
NM_000244.4:c.545T>G
NM_001370251.2:c.530T>G
NM_001370259.2:c.530T>GMANE SELECT
NM_001370260.2:c.530T>G
NM_001370261.2:c.530T>G
NM_001370262.2:c.530T>G
NM_001370263.2:c.530T>G
NM_001407142.1:c.530T>G
NM_001407143.1:c.530T>G
NM_001407144.1:c.530T>G
NM_001407145.1:c.545T>G
NM_001407146.1:c.530T>G
NM_001407147.1:c.530T>G
NM_001407148.1:c.530T>G
NM_001407149.1:c.530T>G
NM_001407150.1:c.545T>G
NM_001407151.1:c.530T>G
NM_001407152.1:c.530T>G
NM_130799.3:c.530T>G
NM_130800.3:c.545T>G
NM_130801.3:c.545T>G
NM_130802.3:c.545T>G
NM_130803.3:c.545T>G
NM_130804.3:c.545T>G
NP_000235.2:p.Leu182Arg
NP_000235.3:p.Leu182Arg
NP_001357180.2:p.Leu177Arg
NP_001357188.2:p.Leu177Arg
NP_001357189.2:p.Leu177Arg
NP_001357190.2:p.Leu177Arg
NP_001357191.2:p.Leu177Arg
NP_001357192.2:p.Leu177Arg
NP_001394071.1:p.Leu177Arg
NP_001394072.1:p.Leu177Arg
NP_001394073.1:p.Leu177Arg
NP_001394074.1:p.Leu182Arg
NP_001394075.1:p.Leu177Arg
NP_001394076.1:p.Leu177Arg
NP_001394077.1:p.Leu177Arg
NP_001394078.1:p.Leu177Arg
NP_001394079.1:p.Leu182Arg
NP_001394080.1:p.Leu177Arg
NP_001394081.1:p.Leu177Arg
NP_570711.1:p.Leu177Arg
NP_570711.2:p.Leu177Arg
NP_570712.2:p.Leu182Arg
NP_570713.2:p.Leu182Arg
NP_570714.2:p.Leu182Arg
NP_570715.2:p.Leu182Arg
NP_570716.2:p.Leu182Arg
LRG_509t1:c.545T>G
LRG_509t2:c.530T>G
LRG_509:g.8280T>G
LRG_509p1:p.Leu182Arg
LRG_509p2:p.Leu177Arg
NC_000011.9:g.64575487A>C
NG_033040.1:g.227T>G
NM_000244.3:c.545T>G
NM_130799.2:c.530T>G
NR_176284.1:n.579T>G
NR_176285.1:n.591T>G
NR_176286.1:n.594T>G
NR_176287.1:n.852T>G

Protein change:

L177R

Molecular consequence:

NM_000244.4:c.545T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001370251.2:c.530T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001370259.2:c.530T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001370260.2:c.530T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001370261.2:c.530T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001370262.2:c.530T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001370263.2:c.530T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407142.1:c.530T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407143.1:c.530T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407144.1:c.530T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407145.1:c.545T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407146.1:c.530T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407147.1:c.530T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407148.1:c.530T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407149.1:c.530T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407150.1:c.545T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407151.1:c.530T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407152.1:c.530T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_130799.3:c.530T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_130800.3:c.545T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_130801.3:c.545T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_130802.3:c.545T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_130803.3:c.545T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_130804.3:c.545T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002646770	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Mar 3, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26288158, 29284071 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002646770

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Mar 3, 2021)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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

Rational Design of Orthogonal Multipolar Interactions with Fluorine in Protein-Ligand Complexes.

Pollock J, Borkin D, Lund G, Purohit T, Dyguda-Kazimierowicz E, Grembecka J, Cierpicki T.

J Med Chem. 2015 Sep 24;58(18):7465-74. doi: 10.1021/acs.jmedchem.5b00975. Epub 2015 Sep 6.

PubMed [citation]

PMID:: 26288158
PMCID:: PMC4584387

Design of the First-in-Class, Highly Potent Irreversible Inhibitor Targeting the Menin-MLL Protein-Protein Interaction.

Xu S, Aguilar A, Xu T, Zheng K, Huang L, Stuckey J, Chinnaswamy K, Bernard D, Fernández-Salas E, Liu L, Wang M, McEachern D, Przybranowski S, Foster C, Wang S.

Angew Chem Int Ed Engl. 2018 Feb 5;57(6):1601-1605. doi: 10.1002/anie.201711828. Epub 2018 Jan 15.

PubMed [citation]

PMID:: 29284071

Details of each submission

From Ambry Genetics, SCV002646770.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The p.L177R variant (also known as c.530T>G), located in coding exon 2 of the MEN1 gene, results from a T to G substitution at nucleotide position 530. The leucine at codon 177 is replaced by arginine, an amino acid with dissimilar properties. This alteration has been observed in at least one individual with a personal and/or family history that is consistent with MEN1 related disease (Ambry internal data). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on internal structural analysis, this variant is anticipated to result in a decrease in structural stability (Ambry internal data; Pollock J et al. J Med Chem, 2015 Sep;58:7465-74; Xu S et al. Angew Chem Int Ed Engl, 2018 02;57:1601-1605). Based on the majority of available evidence to date, this variant is likely to be 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: May 1, 2024

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