NM_000249.4(MLH1):c.2103G>C (p.Gln701His) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jul 31, 2024
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:: RCV003477468.2

Allele description [Variation Report for NM_000249.4(MLH1):c.2103G>C (p.Gln701His)]

NM_000249.4(MLH1):c.2103G>C (p.Gln701His)

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.2103G>C (p.Gln701His)

HGVS:

NC_000003.12:g.37049017G>C
NG_007109.2:g.60668G>C
NM_000249.4:c.2103G>CMANE SELECT
NM_001167617.3:c.1809G>C
NM_001167618.3:c.1380G>C
NM_001167619.3:c.1380G>C
NM_001258271.2:c.1896+1334G>C
NM_001258273.2:c.1380G>C
NM_001258274.3:c.1380G>C
NM_001354615.2:c.1380G>C
NM_001354616.2:c.1380G>C
NM_001354617.2:c.1380G>C
NM_001354618.2:c.1380G>C
NM_001354619.2:c.1380G>C
NM_001354620.2:c.1809G>C
NM_001354621.2:c.1080G>C
NM_001354622.2:c.1080G>C
NM_001354623.2:c.1080G>C
NM_001354624.2:c.1029G>C
NM_001354625.2:c.1029G>C
NM_001354626.2:c.1029G>C
NM_001354627.2:c.1029G>C
NM_001354628.2:c.2010G>C
NM_001354629.2:c.2004G>C
NM_001354630.2:c.1938G>C
NP_000240.1:p.Gln701His
NP_000240.1:p.Gln701His
NP_001161089.1:p.Gln603His
NP_001161090.1:p.Gln460His
NP_001161091.1:p.Gln460His
NP_001245202.1:p.Gln460His
NP_001245203.1:p.Gln460His
NP_001341544.1:p.Gln460His
NP_001341545.1:p.Gln460His
NP_001341546.1:p.Gln460His
NP_001341547.1:p.Gln460His
NP_001341548.1:p.Gln460His
NP_001341549.1:p.Gln603His
NP_001341550.1:p.Gln360His
NP_001341551.1:p.Gln360His
NP_001341552.1:p.Gln360His
NP_001341553.1:p.Gln343His
NP_001341554.1:p.Gln343His
NP_001341555.1:p.Gln343His
NP_001341556.1:p.Gln343His
NP_001341557.1:p.Gln670His
NP_001341558.1:p.Gln668His
NP_001341559.1:p.Gln646His
LRG_216t1:c.2103G>C
LRG_216:g.60668G>C
LRG_216p1:p.Gln701His
NC_000003.11:g.37090508G>C
NM_000249.3:c.2103G>C

Protein change:

Q343H

Links:

dbSNP: rs63750603

NCBI 1000 Genomes Browser:

rs63750603

Molecular consequence:

NM_001258271.2:c.1896+1334G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000249.4:c.2103G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001167617.3:c.1809G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001167618.3:c.1380G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001167619.3:c.1380G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001258273.2:c.1380G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001258274.3:c.1380G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354615.2:c.1380G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354616.2:c.1380G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354617.2:c.1380G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354618.2:c.1380G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354619.2:c.1380G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354620.2:c.1809G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354621.2:c.1080G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354622.2:c.1080G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354623.2:c.1080G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354624.2:c.1029G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354625.2:c.1029G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354626.2:c.1029G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354627.2:c.1029G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354628.2:c.2010G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354629.2:c.2004G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354630.2:c.1938G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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manganese lipoxygenase [Nannochloropsis gaditana]
manganese lipoxygenase [Nannochloropsis gaditana]
gi|585107494|gb|EWM25661.1||gnl|WGS |Naga_100546g4.2628

Protein
RecName: Full=Manganese lipoxygenase; Short=Mn-LO; Short=MnLOX; AltName: Full=Li...
RecName: Full=Manganese lipoxygenase; Short=Mn-LO; Short=MnLOX; AltName: Full=Linoleate 11S-lipoxygenase; AltName: Full=Linoleate 13R-lipoxygenase; AltName: Full=Manganese 13R-lipoxygenase; Short=13R-MnLOX; Flags: Precursor
gi|1027923709|sp|Q8X150.2|MNLOX_GAE

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004220872	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (May 16, 2023)	unknown	clinical testing	PubMed (13) [See all records that cite these PMIDs] 16341550, 16216036, 15849733, 30521064, 21404117, 17192056, 36593122, 32849802, 32661327, 31118792, 30212499, 31491536, 26467025
SCV005090589	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 31, 2024)	germline	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

SCV004220872

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Pathogenic
(May 16, 2023)

unknown

clinical testing

PubMed (13)
[See all records that cite these PMIDs]

SCV005090589

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jul 31, 2024)

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	unknown	unknown	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

Citations

PubMed

Aberrant splicing in MLH1 and MSH2 due to exonic and intronic variants.

Pagenstecher C, Wehner M, Friedl W, Rahner N, Aretz S, Friedrichs N, Sengteller M, Henn W, Buettner R, Propping P, Mangold E.

Hum Genet. 2006 Mar;119(1-2):9-22. Epub 2005 Dec 8.

PubMed [citation]

PMID:: 16341550

Tumours from MSH2 mutation carriers show loss of MSH2 expression but many tumours from MLH1 mutation carriers exhibit weak positive MLH1 staining.

Mangold E, Pagenstecher C, Friedl W, Fischer HP, Merkelbach-Bruse S, Ohlendorf M, Friedrichs N, Aretz S, Buettner R, Propping P, Mathiak M.

J Pathol. 2005 Dec;207(4):385-95.

PubMed [citation]

PMID:: 16216036

See all PubMed Citations (14)

Details of each submission

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV004220872.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (13)

Description

The MLH1 c.2103G>C (p.Gln701His) variant (also known as Q701H) has been reported in the published literature in individuals and families affected with colorectal cancer (PMIDs: 16216036 (2005), 16341550 (2006), 21404117 (2011), 30521064 (2019), 31491536 (2020)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Studies of RNA splicing and immunohistochemistry in tumors have shown that this variant causes complete exon skipping and loss of MLH1 expression (PMIDs: 15849733 (2005), 16216036 (2005), 16341550 (2006), 36593122 (2023)). Based on the available information, this variant is classified as pathogenic.

#	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 Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, SCV005090589.1

#	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	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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