DisGeNET - a database of gene-disease associations

Hereditary Nonpolyposis Colorectal Cancer, C1333990

Gene: MLH1 ×

Source: ALL

Results per page

Gene

Disease

Variant

Source

Association Type

Semantic type

Protein Class

Disease Class

Type

Original DB

Consequence

DSI _v

DPI _v

pLI

EI _vda

EL _gda

Score _vda

PMID

PMID Year

AF_EXOME

Num. PMIDs

Num. SNPs_gda

AF_GENOME

Variant

Gene

Risk Allele

Score _vda

Association Type

Original DB

Sentence supporting the association

PMID

PMID Year

dbSNP:

rs63751713

MLH1

0.020

GeneticVariation

BEFREE

Analysis of seven HNPCC-associated hMLH1 missense mutations located within the hMRE11-interacting domain shows that four mutations (L574P, K618T, R659P and A681T) cause near-complete disruption of the interaction between hMRE11 and hMLH1, and two mutations (Q542L and L582V) cause a 30% reduction of protein interaction.

15864295

2005

dbSNP:

rs1060504000

MLH1

0.010

GeneticVariation

BEFREE

We aimed to determine the pathogenicity of previously reported variants (c.-28A>G and c.-7C>T) within the MLH1 5'untranslated region (UTR) in two individuals from unrelated suspected Lynch syndrome families.

25762362

2015

dbSNP:

rs1260021106

MLH1

0.010

GeneticVariation

BEFREE

25762362

2015

dbSNP:

rs1392665848

MLH1

0.010

GeneticVariation

BEFREE

We encountered a large Irish Lynch syndrome kindred that carries the c.544A>G (p.Arg182Gly) alteration in the MLH1 gene and we undertook to study the variant.

22773173

2012

dbSNP:

rs267607713

MLH1

0.010

GeneticVariation

BEFREE

Detailed characterization of MLH1 p.D41H and p.N710D variants coexisting in a Lynch syndrome family with conserved MLH1 expression tumors.

25060679

2015

dbSNP:

rs28930073

MLH1

0.010

GeneticVariation

BEFREE

Here, we describe a family that does not meet the international criteria for HNPCC, of which a young woman harbors a missense mutation (D132H).

16685411

2006

dbSNP:

rs35045067

MLH1

0.010

GeneticVariation

BEFREE

The pathogenicity of the K618A and Y646C mutations was questionable as their correlation with features typical of HNPCC was low and the outcome of the functional analysis was ambiguous.

16724012

2006

dbSNP:

rs376642306

MLH1

0.010

GeneticVariation

BEFREE

In this study, we show segregation of the putative pathogenic MSH6 missense mutation c.1346T>C p.Leu449Pro with microsatellite instability-high Lynch syndrome-related tumours lacking MSH6 expression in a large 17th century pedigree.

16283884

2005

dbSNP:

rs41295282

MLH1

0.010

GeneticVariation

BEFREE

In contrast, the third amino-terminal mutation S93G did not affect the heterodimerization, and the MLH1(S93G)/PMS2 variant was functional in the in vitro MMR assay, given thus the nature of the HNPCC family in question.

11793442

2002

dbSNP:

rs41295284

MLH1

0.010

GeneticVariation

BEFREE

This outcome could explain the HNPCC familial cancers that present as microsatellite stable and with intact MMR, such as MLH(L607H).

20978114

2010

dbSNP:

rs63750193

MLH1

0.010

GeneticVariation

BEFREE

16283884

2005

dbSNP:

rs63750511

MLH1

0.010

GeneticVariation

BEFREE

Interestingly, two HNPCC missense alterations (Q542L and L582V) contained within the consensus interaction region displayed no effect on interaction with hPMS2, suggesting that they may affect other functions of hMLH1.

10037723

1999

dbSNP:

rs63750575

MLH1

0.010

GeneticVariation

BEFREE

Evidence from clinical, histological, immunohistochemical, and molecular genetic data suggests that MLH1 c.1664T>C (p.Leu555Pro) is likely to be the pathogenic cause of Lynch syndrome in this family.

23712482

2013

dbSNP:

rs63750656

MLH1 ; EPM2AIP1

0.010

GeneticVariation

BEFREE

A dominantly transmitted constitutional MLH1 epimutation has been linked to an MLH1 haplotype bearing two single-nucleotide variants, NM_000249.2: c.-27C>A and c.85G>T, in a Caucasian family with Lynch syndrome from Western Australia.

24084575

2014

dbSNP:

rs63750791

MLH1

0.010

GeneticVariation

BEFREE

The silent mutation MLH1 c.543C>T resulting in aberrant splicing can cause Lynch syndrome: a case report.

28334867

2017

dbSNP:

rs63751202

MLH1

0.010

GeneticVariation

BEFREE

Evidence from clinical, histological, immunohistochemical, and molecular genetic data suggests that MLH1 c.1664T>C (p.Leu555Pro) is likely to be the pathogenic cause of Lynch syndrome in this family.

23712482

2013

dbSNP:

rs780406337

MLH1

0.010

GeneticVariation

BEFREE

Both mutations: c.3984_3987dup and c.1906G>C account for 61% of HNPCC Ashkenazi families in this cohort.

19851887

2010

dbSNP:

rs786201226

MLH1

0.010

GeneticVariation

BEFREE

25762362

2015

dbSNP:

rs864622258

MLH1

0.010

GeneticVariation

BEFREE

We herein describe a nucleotide change, c.2063T>G in exon 13 of the MSH2 gene, present in families that fulfill the Amsterdam criteria for Lynch syndrome and originate from northern Tenerife (Canary Islands-Spain).

16500024

2006

dbSNP:

rs63750206

MLH1

0.720

CausalMutation

CLINVAR

Functional analysis of human MLH1 mutations in Saccharomyces cerevisiae.

9697702

1998

dbSNP:

rs63750206

MLH1

0.720

CausalMutation

CLINVAR

Clinical and genetic characteristics of Chinese hereditary nonpolyposis colorectal cancer families.

16810763

2006

dbSNP:

rs63750206

MLH1

0.720

CausalMutation

CLINVAR

Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database.

24362816

2014

dbSNP:

rs63750206

MLH1

0.720

CausalMutation

CLINVAR

Genetic characterization of Chinese hereditary non-polyposis colorectal cancer by DHPLC and multiplex PCR.

15613555

2004

dbSNP:

rs63750206

MLH1

0.720

CausalMutation

CLINVAR

Molecular analysis of hereditary nonpolyposis colorectal cancer in the United States: high mutation detection rate among clinically selected families and characterization of an American founder genomic deletion of the MSH2 gene.

12658575

2003

dbSNP:

rs63750206

MLH1

0.720

CausalMutation

CLINVAR

Mutation screening in the hMLH1 gene in Swedish hereditary nonpolyposis colon cancer families.

8521398

1995