NM_000249.4(MLH1):c.2101C>A (p.Gln701Lys) AND Colorectal cancer, hereditary nonpolyposis, type 2

Germline classification:: Conflicting interpretations of pathogenicity (4 submissions)
Last evaluated:: Jul 7, 2023
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:: RCV000490357.9

Allele description [Variation Report for NM_000249.4(MLH1):c.2101C>A (p.Gln701Lys)]

NM_000249.4(MLH1):c.2101C>A (p.Gln701Lys)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000249.4(MLH1):c.2101C>A (p.Gln701Lys)

Other names:

p.Q701K:CAG>AAG

HGVS:

NC_000003.12:g.37049015C>A
NG_007109.2:g.60666C>A
NM_000249.4:c.2101C>AMANE SELECT
NM_001167617.3:c.1807C>A
NM_001167618.3:c.1378C>A
NM_001167619.3:c.1378C>A
NM_001258271.2:c.1896+1332C>A
NM_001258273.2:c.1378C>A
NM_001258274.3:c.1378C>A
NM_001354615.2:c.1378C>A
NM_001354616.2:c.1378C>A
NM_001354617.2:c.1378C>A
NM_001354618.2:c.1378C>A
NM_001354619.2:c.1378C>A
NM_001354620.2:c.1807C>A
NM_001354621.2:c.1078C>A
NM_001354622.2:c.1078C>A
NM_001354623.2:c.1078C>A
NM_001354624.2:c.1027C>A
NM_001354625.2:c.1027C>A
NM_001354626.2:c.1027C>A
NM_001354627.2:c.1027C>A
NM_001354628.2:c.2008C>A
NM_001354629.2:c.2002C>A
NM_001354630.2:c.1936C>A
NP_000240.1:p.Gln701Lys
NP_000240.1:p.Gln701Lys
NP_001161089.1:p.Gln603Lys
NP_001161090.1:p.Gln460Lys
NP_001161091.1:p.Gln460Lys
NP_001245202.1:p.Gln460Lys
NP_001245203.1:p.Gln460Lys
NP_001341544.1:p.Gln460Lys
NP_001341545.1:p.Gln460Lys
NP_001341546.1:p.Gln460Lys
NP_001341547.1:p.Gln460Lys
NP_001341548.1:p.Gln460Lys
NP_001341549.1:p.Gln603Lys
NP_001341550.1:p.Gln360Lys
NP_001341551.1:p.Gln360Lys
NP_001341552.1:p.Gln360Lys
NP_001341553.1:p.Gln343Lys
NP_001341554.1:p.Gln343Lys
NP_001341555.1:p.Gln343Lys
NP_001341556.1:p.Gln343Lys
NP_001341557.1:p.Gln670Lys
NP_001341558.1:p.Gln668Lys
NP_001341559.1:p.Gln646Lys
LRG_216t1:c.2101C>A
LRG_216:g.60666C>A
LRG_216p1:p.Gln701Lys
NC_000003.11:g.37090506C>A
NM_000249.3:c.2101C>A
p.Q701K

Protein change:

Q343K

Links:

dbSNP: rs63750114

NCBI 1000 Genomes Browser:

rs63750114

Molecular consequence:

NM_001258271.2:c.1896+1332C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000249.4:c.2101C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001167617.3:c.1807C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001167618.3:c.1378C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001167619.3:c.1378C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001258273.2:c.1378C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001258274.3:c.1378C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354615.2:c.1378C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354616.2:c.1378C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354617.2:c.1378C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354618.2:c.1378C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354619.2:c.1378C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354620.2:c.1807C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354621.2:c.1078C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354622.2:c.1078C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354623.2:c.1078C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354624.2:c.1027C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354625.2:c.1027C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354626.2:c.1027C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354627.2:c.1027C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354628.2:c.2008C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354629.2:c.2002C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354630.2:c.1936C>A - missense variant - [Sequence Ontology: SO:0001583]

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

Recent activity

Clear Turn Off Turn On

EC2CAA11CG04.g1 Xenopus tropicalis xthr plasmid library Xenopus tropicalis cDNA ...
EC2CAA11CG04.g1 Xenopus tropicalis xthr plasmid library Xenopus tropicalis cDNA clone xthr11N07 5', mRNA sequence
gi|45889268|gnl|dbEST|22209761|gb|C 72.1|

Nucleotide
AL955989 XGC-gastrula Xenopus tropicalis cDNA clone TGas124o12 5', mRNA sequence
AL955989 XGC-gastrula Xenopus tropicalis cDNA clone TGas124o12 5', mRNA sequence
gi|38705475|gnl|dbEST|20728316|emb| 989.2|

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000267396	Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 18, 2016)	germline	reference population	PubMed (3) [See all records that cite these PMIDs] 16929514, 18094436, 25741868
SCV001136435	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Benign (May 28, 2019)	unknown	clinical testing	Citation Link,
SCV001307915	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Apr 28, 2017)	germline	clinical testing	PubMed (14) [See all records that cite these PMIDs] 17011982, 18094436, 26811195, 26900293, 26078562, 26332594, 24933000, 23431106, 22995991, 22136435, 18726168, 23760103, 16929514, 18931482 Citation Link,
SCV004015886	KCCC/NGS Laboratory, Kuwait Cancer Control Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Jul 7, 2023)	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	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
East Asian	germline	unknown	1	not provided	not provided	not provided	not provided	reference population

Citations

PubMed

Variations in exon 7 of the MSH2 gene and susceptibility to gastrointestinal cancer in a Chinese population.

Fan Y, Liu X, Zhang H, Dai J, Zhang X, Zhu M, Gao X, Wang Y.

Cancer Genet Cytogenet. 2006 Oct 15;170(2):121-8.

PubMed [citation]

PMID:: 17011982

Analysis of hMLH1 missense mutations in East Asian patients with suspected hereditary nonpolyposis colorectal cancer.

Fan Y, Wang W, Zhu M, Zhou J, Peng J, Xu L, Hua Z, Gao X, Wang Y.

Clin Cancer Res. 2007 Dec 15;13(24):7515-21.

PubMed [citation]

PMID:: 18094436

See all PubMed Citations (15)

Details of each submission

From Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center, SCV000267396.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	East Asian	1	not provided	not provided	reference population	PubMed (3)

#	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		1	not provided	not provided	not provided

From Mendelics, SCV001136435.1

#	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 Illumina Laboratory Services, Illumina, SCV001307915.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (14)

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). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

#	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 KCCC/NGS Laboratory, Kuwait Cancer Control Center, SCV004015886.1

#	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

Last Updated: Oct 13, 2024

ClinVar

Relating variation to medicine