NM_001370259.2(MEN1):c.1409C>T (p.Pro470Leu) AND Multiple endocrine neoplasia, type 1

Germline classification:: Conflicting interpretations of pathogenicity (5 submissions)
Last evaluated:: Feb 1, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV000167949.24

Allele description [Variation Report for NM_001370259.2(MEN1):c.1409C>T (p.Pro470Leu)]

NM_001370259.2(MEN1):c.1409C>T (p.Pro470Leu)

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.1409C>T (p.Pro470Leu)

HGVS:

NC_000011.10:g.64804758G>A
NG_008929.1:g.11537C>T
NG_033040.1:g.3484C>T
NM_000244.4:c.1424C>T
NM_001370251.2:c.1535C>T
NM_001370259.2:c.1409C>TMANE SELECT
NM_001370260.2:c.1409C>T
NM_001370261.2:c.1409C>T
NM_001370262.2:c.1304C>T
NM_001370263.2:c.1304C>T
NM_130799.3:c.1409C>T
NM_130800.3:c.1424C>T
NM_130801.3:c.1424C>T
NM_130802.3:c.1424C>T
NM_130803.3:c.1424C>T
NM_130804.3:c.1424C>T
NP_000235.2:p.Pro475Leu
NP_000235.3:p.Pro475Leu
NP_001357180.2:p.Pro512Leu
NP_001357188.2:p.Pro470Leu
NP_001357189.2:p.Pro470Leu
NP_001357190.2:p.Pro470Leu
NP_001357191.2:p.Pro435Leu
NP_001357192.2:p.Pro435Leu
NP_570711.1:p.Pro470Leu
NP_570711.2:p.Pro470Leu
NP_570712.2:p.Pro475Leu
NP_570713.2:p.Pro475Leu
NP_570714.2:p.Pro475Leu
NP_570715.2:p.Pro475Leu
NP_570716.2:p.Pro475Leu
LRG_509t1:c.1424C>T
LRG_509t2:c.1409C>T
LRG_509:g.11537C>T
LRG_509p1:p.Pro475Leu
LRG_509p2:p.Pro470Leu
NC_000011.9:g.64572230G>A
NM_000244.3:c.1424C>T
NM_130799.2:c.1409C>T

Protein change:

P435L

Links:

dbSNP: rs750112288

NCBI 1000 Genomes Browser:

rs750112288

Molecular consequence:

NM_000244.4:c.1424C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001370251.2:c.1535C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001370259.2:c.1409C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001370260.2:c.1409C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001370261.2:c.1409C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001370262.2:c.1304C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001370263.2:c.1304C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_130799.3:c.1409C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_130800.3:c.1424C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_130801.3:c.1424C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_130802.3:c.1424C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_130803.3:c.1424C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_130804.3:c.1424C>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
SCV000218597	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Benign (Feb 1, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000488097	Counsyl	criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015))	Likely benign (Dec 23, 2015)	unknown	clinical testing	Counsyl Autosomal Dominant Disease Classification criteria (2015), Citation Link,
SCV000781724	Center for Human Genetics, Inc, Center for Human Genetics, Inc	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Nov 1, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001262166	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Benign (Jun 7, 2018)	germline	clinical testing	Citation Link,
SCV004018040	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Uncertain significance (Apr 17, 2023)	unknown	clinical testing	Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	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

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000218597.13

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

From Counsyl, SCV000488097.2

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

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

From Center for Human Genetics, Inc, Center for Human Genetics, Inc, SCV000781724.1

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

From Illumina Laboratory Services, Illumina, SCV001262166.1

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

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.

#	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

From Myriad Genetics, Inc., SCV004018040.1

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

Description

This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.

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

Last Updated: Sep 29, 2024

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