NM_000249.3(MLH1):c.1846_1848AAG[2] (p.Lys618del) AND Lynch syndrome II

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Apr 20, 2016
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:: RCV000192399.2

Allele description

NM_000249.3(MLH1):c.1846_1848AAG[2] (p.Lys618del)

Gene:

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

Variant type:

Microsatellite

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000249.3(MLH1):c.1846_1848AAG[2] (p.Lys618del)

Other names:

MLH1, 3-BP DEL, LYS618DEL

HGVS:

NC_000003.12:g.37047633_37047635AAG[2]
NG_007109.2:g.59284_59286AAG[2]
NM_000249.3:c.1846_1848AAG[2]
NM_001167617.2:c.1552_1554AAG[2]
NM_001167618.2:c.1123_1125AAG[2]
NM_001167619.2:c.1123_1125AAG[2]
NM_001258271.1:c.1846_1848AAG[2]
NM_001258273.1:c.1123_1125AAG[2]
NM_001258274.2:c.1123_1125AAG[2]
NM_001354615.1:c.1123_1125AAG[2]
NM_001354616.1:c.1123_1125AAG[2]
NM_001354617.1:c.1123_1125AAG[2]
NM_001354618.1:c.1123_1125AAG[2]
NM_001354619.1:c.1123_1125AAG[2]
NM_001354620.1:c.1552_1554AAG[2]
NM_001354621.1:c.823_825AAG[2]
NM_001354622.1:c.823_825AAG[2]
NM_001354623.1:c.823_825AAG[2]
NM_001354624.1:c.772_774AAG[2]
NM_001354625.1:c.772_774AAG[2]
NM_001354626.1:c.772_774AAG[2]
NM_001354627.1:c.772_774AAG[2]
NM_001354628.1:c.1846_1848AAG[2]
NM_001354629.1:c.1747_1749AAG[2]
NM_001354630.1:c.1732-885GAA[2]
NP_000240.1:p.Lys618del
NP_001161089.1:p.Lys520del
NP_001161090.1:p.Lys377del
NP_001161091.1:p.Lys377del
NP_001245200.1:p.Lys618del
NP_001245202.1:p.Lys377del
NP_001245203.1:p.Lys377del
NP_001341544.1:p.Lys377del
NP_001341545.1:p.Lys377del
NP_001341546.1:p.Lys377del
NP_001341547.1:p.Lys377del
NP_001341548.1:p.Lys377del
NP_001341549.1:p.Lys520del
NP_001341550.1:p.Lys277del
NP_001341551.1:p.Lys277del
NP_001341552.1:p.Lys277del
NP_001341553.1:p.Lys260del
NP_001341554.1:p.Lys260del
NP_001341555.1:p.Lys260del
NP_001341556.1:p.Lys260del
NP_001341557.1:p.Lys618del
NP_001341558.1:p.Lys585del
LRG_216t1:c.1852_1854del
LRG_216:g.59284_59286AAG[2]
LRG_216p1:p.Lys618del
NC_000003.11:g.37089124_37089126AAG[2]
NC_000003.11:g.37089130_37089132delAAG
NM_000249.3:c.1852_1854delAAG
p.K616del
p.K618del

Protein change:

K375del; LYS616DEL

Links:

OMIM: 120436.0003; OMIM: 120436.0018; dbSNP: rs63751247

NCBI 1000 Genomes Browser:

rs63751247

Molecular consequence:

NM_001167617.2:c.1552_1554AAG[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001167618.2:c.1123_1125AAG[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001167619.2:c.1123_1125AAG[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001258271.1:c.1846_1848AAG[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001258273.1:c.1123_1125AAG[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001258274.2:c.1123_1125AAG[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001354615.1:c.1123_1125AAG[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001354616.1:c.1123_1125AAG[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001354617.1:c.1123_1125AAG[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001354618.1:c.1123_1125AAG[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001354619.1:c.1123_1125AAG[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001354620.1:c.1552_1554AAG[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001354621.1:c.823_825AAG[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001354622.1:c.823_825AAG[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001354623.1:c.823_825AAG[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001354624.1:c.772_774AAG[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001354625.1:c.772_774AAG[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001354626.1:c.772_774AAG[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001354627.1:c.772_774AAG[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001354628.1:c.1846_1848AAG[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001354629.1:c.1747_1749AAG[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001354630.1:c.1732-885GAA[2] - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Lynch syndrome II (HNPCC2)
Synonyms:: COLON CANCER, FAMILIAL NONPOLYPOSIS, TYPE 2; MLH1-Related Hereditary Non-Polyposis Colon Cancer; MLH1-Related Lynch Syndrome
Identifiers:: MedGen: C1333991; Orphanet: 144; OMIM: 609310

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000038910	OMIM	no assertion criteria provided	Pathogenic (Apr 1, 2009)	germline	literature only	PubMed (3) [See all records that cite these PMIDs] 14635101, 8581513, 19419416
SCV000248052	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 5, 2014)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000488529	Counsyl	criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015))	Pathogenic (Apr 20, 2016)	unknown	clinical testing	PubMed (5) [See all records that cite these PMIDs] 17453009, 12891553, 17510385, 24362816, 22949379 Counsyl Autosomal Dominant Disease Classification criteria (2015) Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000038910

OMIM

no assertion criteria provided

Pathogenic
(Apr 1, 2009)

germline

literature only

PubMed (3)
[See all records that cite these PMIDs]

SCV000248052

Genetic Services Laboratory, University of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Dec 5, 2014)

germline

clinical testing

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

SCV000488529

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Dominant Disease Classification criteria (2015))

Pathogenic
(Apr 20, 2016)

unknown

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Counsyl Autosomal Dominant Disease Classification criteria (2015)

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	yes	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

Genomic deletions in MSH2 or MLH1 are a frequent cause of hereditary non-polyposis colorectal cancer: identification of novel and recurrent deletions by MLPA.

Taylor CF, Charlton RS, Burn J, Sheridan E, Taylor GR.

Hum Mutat. 2003 Dec;22(6):428-33.

PubMed [citation]

PMID:: 14635101

Germ line mutations of hMSH2 and hMLH1 genes in Japanese families with hereditary nonpolyposis colorectal cancer (HNPCC): usefulness of DNA analysis for screening and diagnosis of HNPCC patients.

Miyaki M, Konishi M, Muraoka M, Kikuchi-Yanoshita R, Tanaka K, Iwama T, Mori T, Koike M, Ushio K, Chiba M, et al.

J Mol Med (Berl). 1995 Oct;73(10):515-20.

PubMed [citation]

PMID:: 8581513

See all PubMed Citations (9)

Details of each submission

From OMIM, SCV000038910.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (3)

Description

In 4 cases of hereditary nonpolyposis colorectal cancer (609310), Taylor et al. (2003) found deletion of 3 nucleotides: 1846-1848delAAG resulting in deletion of lys616 (K616del) from the MLH1 protein. This mutation had been previously observed by Miyaki et al. (1995). Taylor et al. (2003) used the multiplex ligation-dependent probe amplification (MLDA) assay to demonstrate the deletion.

Tang et al. (2009) identified a heterozygous 1846delAAG mutation in affected members of 5 Taiwanese families with HNPCC2.

#	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 Genetic Services Laboratory, University of Chicago, SCV000248052.1

#	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 Counsyl, SCV000488529.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

#	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 1, 2019

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