NM_000249.4(MLH1):c.210AGA[1] (p.Glu71del) AND Colorectal cancer, hereditary nonpolyposis, type 2

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Aug 20, 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:: RCV000018633.26

Allele description [Variation Report for NM_000249.4(MLH1):c.210AGA[1] (p.Glu71del)]

NM_000249.4(MLH1):c.210AGA[1] (p.Glu71del)

Gene:

MLH1:mutL homolog 1 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000249.4(MLH1):c.210AGA[1] (p.Glu71del)

HGVS:

NC_000003.12:g.37000957AGA[1]
NG_007109.2:g.12608AGA[1]
NM_000249.4:c.210AGA[1]MANE SELECT
NM_001167617.3:c.-80AGA[1]
NM_001167618.3:c.-514AGA[1]
NM_001167619.3:c.-422AGA[1]
NM_001258271.2:c.210AGA[1]
NM_001258273.2:c.-514AGA[1]
NM_001258274.3:c.-514AGA[1]
NM_001354615.2:c.-417AGA[1]
NM_001354616.2:c.-422AGA[1]
NM_001354617.2:c.-514AGA[1]
NM_001354618.2:c.-514AGA[1]
NM_001354619.2:c.-514AGA[1]
NM_001354620.2:c.-80AGA[1]
NM_001354621.2:c.-607AGA[1]
NM_001354622.2:c.-720AGA[1]
NM_001354623.2:c.-720AGA[1]
NM_001354624.2:c.-617AGA[1]
NM_001354625.2:c.-520AGA[1]
NM_001354626.2:c.-617AGA[1]
NM_001354627.2:c.-617AGA[1]
NM_001354628.2:c.210AGA[1]
NM_001354629.2:c.208-3441_208-3439del
NM_001354630.2:c.210AGA[1]
NP_000240.1:p.Glu71del
NP_001245200.1:p.Glu71del
NP_001341557.1:p.Glu71del
NP_001341559.1:p.Glu71del
LRG_216t1:c.213_215del
LRG_216:g.12608AGA[1]
NC_000003.11:g.37042447_37042449del
NC_000003.11:g.37042448AGA[1]
NM_000249.3:c.213_215del
NM_000249.3:c.213_215delAGA
NM_000249.4:c.213_215delMANE SELECT

Protein change:

E71del

Links:

LOVD 3: MLH1_000141; OMIM: 120436.0023; dbSNP: rs63751642

NCBI 1000 Genomes Browser:

rs63751642

Molecular consequence:

NM_001167617.3:c.-80AGA[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167618.3:c.-514AGA[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167619.3:c.-422AGA[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258273.2:c.-514AGA[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258274.3:c.-514AGA[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354615.2:c.-417AGA[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354616.2:c.-422AGA[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354617.2:c.-514AGA[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354618.2:c.-514AGA[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354619.2:c.-514AGA[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354620.2:c.-80AGA[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354621.2:c.-607AGA[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354622.2:c.-720AGA[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354623.2:c.-720AGA[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354624.2:c.-617AGA[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354625.2:c.-520AGA[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354626.2:c.-617AGA[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354627.2:c.-617AGA[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000249.4:c.210AGA[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001258271.2:c.210AGA[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001354628.2:c.210AGA[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001354630.2:c.210AGA[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001354629.2:c.208-3441_208-3439del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Colorectal cancer, hereditary nonpolyposis, type 2 (LYNCH2)
Synonyms:: COLON CANCER, FAMILIAL NONPOLYPOSIS, TYPE 2; Lynch syndrome II; MLH1-Related Lynch Syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0012249; MedGen: C1333991; Orphanet: 144; OMIM: 609310

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000038916	OMIM	no assertion criteria provided	Pathogenic (Feb 1, 2006)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV004190642	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 20, 2023)	unknown	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

SCV000038916

OMIM

no assertion criteria provided

Pathogenic
(Feb 1, 2006)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

SCV004190642

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Aug 20, 2023)

unknown

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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Disruption of an exon splicing enhancer in exon 3 of MLH1 is the cause of HNPCC in a Quebec family.

McVety S, Li L, Gordon PH, Chong G, Foulkes WD.

J Med Genet. 2006 Feb;43(2):153-6. Epub 2005 May 27.

PubMed [citation]

PMID:: 15923275
PMCID:: PMC2564635

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 OMIM, SCV000038916.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

McVety et al. (2006) demonstrated the presence of an exon splicing enhancer (ESE) in exon 3 of MLH1 and showed that a 3-bp in-frame deletion (213_215delAGA) in this ESE was the cause of hereditary nonpolyposis colorectal cancer (LYNCH2; 609310) in a Quebec family. The deletion resulted in loss of codon 71 and caused skipping of exon 3 during mRNA splicing.

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

From Baylor Genetics, SCV004190642.1

#	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	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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