NM_001370259.2(MEN1):c.65T>G (p.Leu22Arg) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 19, 2021
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:: RCV000182402.5

Allele description [Variation Report for NM_001370259.2(MEN1):c.65T>G (p.Leu22Arg)]

NM_001370259.2(MEN1):c.65T>G (p.Leu22Arg)

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.65T>G (p.Leu22Arg)

Other names:

p.L22R:CTG>CGG

HGVS:

NC_000011.10:g.64810045A>C
NG_008929.1:g.6250T>G
NM_000244.4:c.65T>G
NM_001370251.2:c.65T>G
NM_001370259.2:c.65T>GMANE SELECT
NM_001370260.2:c.65T>G
NM_001370261.2:c.65T>G
NM_001370262.2:c.65T>G
NM_001370263.2:c.65T>G
NM_130799.3:c.65T>G
NM_130800.3:c.65T>G
NM_130801.3:c.65T>G
NM_130802.3:c.65T>G
NM_130803.3:c.65T>G
NM_130804.3:c.65T>G
NP_000235.2:p.Leu22Arg
NP_000235.3:p.Leu22Arg
NP_001357180.2:p.Leu22Arg
NP_001357188.2:p.Leu22Arg
NP_001357189.2:p.Leu22Arg
NP_001357190.2:p.Leu22Arg
NP_001357191.2:p.Leu22Arg
NP_001357192.2:p.Leu22Arg
NP_570711.1:p.Leu22Arg
NP_570711.2:p.Leu22Arg
NP_570712.2:p.Leu22Arg
NP_570713.2:p.Leu22Arg
NP_570714.2:p.Leu22Arg
NP_570715.2:p.Leu22Arg
NP_570716.2:p.Leu22Arg
LRG_509t1:c.65T>G
LRG_509t2:c.65T>G
LRG_509:g.6250T>G
LRG_509p1:p.Leu22Arg
LRG_509p2:p.Leu22Arg
NC_000011.9:g.64577517A>C
NM_000244.3:c.65T>G
NM_130799.2:c.65T>G
O00255:p.Leu22Arg

Protein change:

L22R; LEU22ARG

Links:

UniProtKB: O00255#VAR_005426; OMIM: 613733.0001; dbSNP: rs104894256

NCBI 1000 Genomes Browser:

rs104894256

Molecular consequence:

NM_000244.4:c.65T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001370251.2:c.65T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001370259.2:c.65T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001370260.2:c.65T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001370261.2:c.65T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001370262.2:c.65T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001370263.2:c.65T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_130799.3:c.65T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_130800.3:c.65T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_130801.3:c.65T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_130802.3:c.65T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_130803.3:c.65T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_130804.3:c.65T>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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Chain A, 5'-R(*CP*GP*UP*AP*CP*DG)-3'
Chain A, 5'-R(*CP*GP*UP*AP*CP*DG)-3'
gi|253722632|pdb|377D|A

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000234745	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Mar 19, 2021)	germline	clinical testing	Citation Link,
SCV001449689	Clinical Genetics and Genomics, Karolinska University Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 6, 2017)	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

SCV000234745

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Mar 19, 2021)

germline

clinical testing

Citation Link,

SCV001449689

Clinical Genetics and Genomics, Karolinska University Hospital

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jul 6, 2017)

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	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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 GeneDx, SCV000234745.9

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

Description

Published functional studies demonstrate a damaging effect: reduced protein expression and stability, inability to repress JunD-mediated transcription or Gas1 expression in Hedgehog signaling (Agarwal et al., 1999; Canaff et al., 2012; Gurung et al., 2013); Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 21264250, 19074834, 22090276, 9989505, 23580576, 9498491, 16195383, 14992727, 17879353, 15281352, 9681840, 9215689, 10730900, 21916912, 21819486, 19596783, 17766243, 20404349, 20639902, 12509449, 22878668, 15640349, 18598942, 21252315, 12112656, 17953629, 9103196, 30869828)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Clinical Genetics and Genomics, Karolinska University Hospital, SCV001449689.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	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	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Feb 20, 2024

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