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NM_001370259.2(MEN1):c.1271AGG[1] (p.Glu425del) AND not provided

Germline classification:
Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:
Nov 14, 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:
RCV002225831.4

Allele description [Variation Report for NM_001370259.2(MEN1):c.1271AGG[1] (p.Glu425del)]

NM_001370259.2(MEN1):c.1271AGG[1] (p.Glu425del)

Gene:
MEN1:menin 1 [Gene - OMIM - HGNC]
Variant type:
Microsatellite
Cytogenetic location:
11q13.1
Genomic location:
Preferred name:
NM_001370259.2(MEN1):c.1271AGG[1] (p.Glu425del)
HGVS:
  • NC_000011.10:g.64805110TCC[1]
  • NC_000011.9:g.64572585_64572587del
  • NG_008929.1:g.11182AGG[1]
  • NG_033040.1:g.3129AGG[1]
  • NM_000244.4:c.1286AGG[1]
  • NM_001370251.2:c.1397AGG[1]
  • NM_001370259.2:c.1271AGG[1]MANE SELECT
  • NM_001370260.2:c.1271AGG[1]
  • NM_001370261.2:c.1271AGG[1]
  • NM_001370262.2:c.1166AGG[1]
  • NM_001370263.2:c.1166AGG[1]
  • NM_130799.3:c.1271AGG[1]
  • NM_130800.3:c.1286AGG[1]
  • NM_130801.3:c.1286AGG[1]
  • NM_130802.3:c.1286AGG[1]
  • NM_130803.3:c.1286AGG[1]
  • NM_130804.3:c.1286AGG[1]
  • NP_000235.3:p.Glu430del
  • NP_001357180.2:p.Glu467del
  • NP_001357188.2:p.Glu425del
  • NP_001357189.2:p.Glu425del
  • NP_001357190.2:p.Glu425del
  • NP_001357191.2:p.Glu390del
  • NP_001357192.2:p.Glu390del
  • NP_570711.2:p.Glu425del
  • NP_570712.2:p.Glu430del
  • NP_570713.2:p.Glu430del
  • NP_570714.2:p.Glu430del
  • NP_570715.2:p.Glu430del
  • NP_570716.2:p.Glu430del
  • LRG_509:g.11182AGG[1]
  • NC_000011.9:g.64572580_64572582del
  • NC_000011.9:g.64572582TCC[1]
  • NC_000011.9:g.64572585_64572587del
  • NM_130799.2:c.1274_1276del
Protein change:
E390del
Links:
dbSNP: rs2136101303
NCBI 1000 Genomes Browser:
rs2136101303
Molecular consequence:
  • NM_000244.4:c.1286AGG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
  • NM_001370251.2:c.1397AGG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
  • NM_001370259.2:c.1271AGG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
  • NM_001370260.2:c.1271AGG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
  • NM_001370261.2:c.1271AGG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
  • NM_001370262.2:c.1166AGG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
  • NM_001370263.2:c.1166AGG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
  • NM_130799.3:c.1271AGG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
  • NM_130800.3:c.1286AGG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
  • NM_130801.3:c.1286AGG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
  • NM_130802.3:c.1286AGG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
  • NM_130803.3:c.1286AGG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
  • NM_130804.3:c.1286AGG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV002504198GeneDx
criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)
Likely pathogenic
(Apr 8, 2022)
germlineclinical testing

Citation Link,

SCV004564588ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process 2024)
Pathogenic
(Nov 14, 2023)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From GeneDx, SCV002504198.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Not observed at significant frequency in large population cohorts (gnomAD); In-frame deletion of 1 amino acid in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; Published functional studies demonstrate a damaging effect: lack of cell growth inhibition, reduced menin expression, and impaired menin function (Hussein 2007, Hussein 2008); Observed in an individual with a personal and family history of MEN1-associated lesions in published literature (Giraud 1998).; This variant is associated with the following publications: (PMID: 17879353, 10730900, 10762295, 11836268, 9683585, 18310289, 12112656, 17184987, 9989505)

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

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV004564588.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The MEN1 c.1274_1276del; p.Glu425del variant (rs2136101303) is reported in the literature in multiple individuals affected with multiple endocrine neoplasia type 1 (Giraud 1998, Wautot 2002). This variant is also reported in ClinVar (Variation ID: 1067928) and is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. Functional analyses of the variant protein show reduced menin function (Hussein 2008). This variant deletes a single glutamic acid residue leaving the rest of the protein in-frame. Based on available information, this variant is considered to be pathogenic. References: Giraud S et al. Germ-line mutation analysis in patients with multiple endocrine neoplasia type 1 and related disorders. Am J Hum Genet. 1998 Aug;63(2):455-67. PMID: 9683585. Hussein N et al. Deregulation of anti-Mullerian hormone/BMP and transforming growth factor-beta pathways in Leydig cell lesions developed in male heterozygous multiple endocrine neoplasia type 1 mutant mice. Endocr Relat Cancer. 2008 Mar;15(1):217-27. PMID: 18310289. Wautot V et al. Germline mutation profile of MEN1 in multiple endocrine neoplasia type 1: search for correlation between phenotype and the functional domains of the MEN1 protein. Hum Mutat. 2002 Jul;20(1):35-47. PMID: 12112656.

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

Last Updated: Sep 29, 2024