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NM_001370259.2(MEN1):c.767T>C (p.Leu256Pro) AND Multiple endocrine neoplasia, type 1

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Apr 26, 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:
RCV003632189.2

Allele description [Variation Report for NM_001370259.2(MEN1):c.767T>C (p.Leu256Pro)]

NM_001370259.2(MEN1):c.767T>C (p.Leu256Pro)

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.767T>C (p.Leu256Pro)
HGVS:
  • NC_000011.10:g.64807568A>G
  • NG_008929.1:g.8727T>C
  • NG_033040.1:g.674T>C
  • NG_033040.2:g.646T>C
  • NM_000244.4:c.782T>C
  • NM_001370251.2:c.767T>C
  • NM_001370259.2:c.767T>CMANE SELECT
  • NM_001370260.2:c.767T>C
  • NM_001370261.2:c.767T>C
  • NM_001370262.2:c.662T>C
  • NM_001370263.2:c.662T>C
  • NM_001407142.1:c.767T>C
  • NM_001407143.1:c.767T>C
  • NM_001407144.1:c.767T>C
  • NM_001407145.1:c.782T>C
  • NM_001407146.1:c.767T>C
  • NM_001407147.1:c.767T>C
  • NM_001407148.1:c.662T>C
  • NM_001407149.1:c.662T>C
  • NM_001407150.1:c.782T>C
  • NM_001407151.1:c.662T>C
  • NM_001407152.1:c.767T>C
  • NM_130799.3:c.767T>C
  • NM_130800.3:c.782T>C
  • NM_130801.3:c.782T>C
  • NM_130802.3:c.782T>C
  • NM_130803.3:c.782T>C
  • NM_130804.3:c.782T>C
  • NP_000235.2:p.Leu261Pro
  • NP_000235.3:p.Leu261Pro
  • NP_001357180.2:p.Leu256Pro
  • NP_001357188.2:p.Leu256Pro
  • NP_001357189.2:p.Leu256Pro
  • NP_001357190.2:p.Leu256Pro
  • NP_001357191.2:p.Leu221Pro
  • NP_001357192.2:p.Leu221Pro
  • NP_001394071.1:p.Leu256Pro
  • NP_001394072.1:p.Leu256Pro
  • NP_001394073.1:p.Leu256Pro
  • NP_001394074.1:p.Leu261Pro
  • NP_001394075.1:p.Leu256Pro
  • NP_001394076.1:p.Leu256Pro
  • NP_001394077.1:p.Leu221Pro
  • NP_001394078.1:p.Leu221Pro
  • NP_001394079.1:p.Leu261Pro
  • NP_001394080.1:p.Leu221Pro
  • NP_001394081.1:p.Leu256Pro
  • NP_570711.1:p.Leu256Pro
  • NP_570711.2:p.Leu256Pro
  • NP_570712.2:p.Leu261Pro
  • NP_570713.2:p.Leu261Pro
  • NP_570714.2:p.Leu261Pro
  • NP_570715.2:p.Leu261Pro
  • NP_570716.2:p.Leu261Pro
  • LRG_509t1:c.782T>C
  • LRG_509t2:c.767T>C
  • LRG_509:g.8727T>C
  • LRG_509p1:p.Leu261Pro
  • LRG_509p2:p.Leu256Pro
  • NC_000011.9:g.64575040A>G
  • NM_000244.3:c.782T>C
  • NM_130799.2:c.767T>C
  • NR_176284.1:n.816T>C
  • NR_176285.1:n.828T>C
  • NR_176286.1:n.831T>C
  • NR_176287.1:n.1089T>C
Protein change:
L221P
Molecular consequence:
  • NM_000244.4:c.782T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001370251.2:c.767T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001370259.2:c.767T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001370260.2:c.767T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001370261.2:c.767T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001370262.2:c.662T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001370263.2:c.662T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407142.1:c.767T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407143.1:c.767T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407144.1:c.767T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407145.1:c.782T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407146.1:c.767T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407147.1:c.767T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407148.1:c.662T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407149.1:c.662T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407150.1:c.782T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407151.1:c.662T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407152.1:c.767T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_130799.3:c.767T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_130800.3:c.782T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_130801.3:c.782T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_130802.3:c.782T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_130803.3:c.782T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_130804.3:c.782T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_176284.1:n.816T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176285.1:n.828T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176286.1:n.831T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176287.1:n.1089T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004460140Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Apr 26, 2023) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Clinical testing for mutations in the MEN1 gene in Sweden: a report on 200 unrelated cases.

Tham E, Grandell U, Lindgren E, Toss G, Skogseid B, Nordenskjöld M.

J Clin Endocrinol Metab. 2007 Sep;92(9):3389-95. Epub 2007 Jul 10.

PubMed [citation]
PMID:
17623761

Multiple endocrine neoplasia type 1: analysis of germline MEN1 mutations in the Italian multicenter MEN1 patient database.

Marini F, Giusti F, Fossi C, Cioppi F, Cianferotti L, Masi L, Boaretto F, Zovato S, Cetani F, Colao A, Davì MV, Faggiano A, Fanciulli G, Ferolla P, Ferone D, Loli P, Mantero F, Marcocci C, Opocher G, Beck-Peccoz P, Persani L, Scillitani A, et al.

Endocrine. 2018 Oct;62(1):215-233. doi: 10.1007/s12020-018-1566-8. Epub 2018 Mar 1. Erratum in: Endocrine. 2018 Oct;62(1):234-241. doi: 10.1007/s12020-018-1668-3.

PubMed [citation]
PMID:
29497973
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004460140.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 256 of the MEN1 protein (p.Leu256Pro). 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. This variant disrupts the p.Leu256 amino acid residue in MEN1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17623761, 29497973, 30374176; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. This variant has not been reported in the literature in individuals affected with MEN1-related conditions. This variant is not present in population databases (gnomAD no frequency).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024