NM_000249.4(MLH1):c.218T>G (p.Leu73Arg) AND Mismatch repair cancer syndrome 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 1, 2013
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000035016.35

Allele description [Variation Report for NM_000249.4(MLH1):c.218T>G (p.Leu73Arg)]

NM_000249.4(MLH1):c.218T>G (p.Leu73Arg)

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.218T>G (p.Leu73Arg)

HGVS:

NC_000003.12:g.37000965T>G
NG_007109.2:g.12616T>G
NM_000249.4:c.218T>GMANE SELECT
NM_001167617.3:c.-72T>G
NM_001167618.3:c.-506T>G
NM_001167619.3:c.-414T>G
NM_001258271.2:c.218T>G
NM_001258273.2:c.-506T>G
NM_001258274.3:c.-506T>G
NM_001354615.2:c.-409T>G
NM_001354616.2:c.-414T>G
NM_001354617.2:c.-506T>G
NM_001354618.2:c.-506T>G
NM_001354619.2:c.-506T>G
NM_001354620.2:c.-72T>G
NM_001354621.2:c.-599T>G
NM_001354622.2:c.-712T>G
NM_001354623.2:c.-712T>G
NM_001354624.2:c.-609T>G
NM_001354625.2:c.-512T>G
NM_001354626.2:c.-609T>G
NM_001354627.2:c.-609T>G
NM_001354628.2:c.218T>G
NM_001354629.2:c.208-3436T>G
NM_001354630.2:c.218T>G
NP_000240.1:p.Leu73Arg
NP_000240.1:p.Leu73Arg
NP_001245200.1:p.Leu73Arg
NP_001341557.1:p.Leu73Arg
NP_001341559.1:p.Leu73Arg
LRG_216t1:c.218T>G
LRG_216:g.12616T>G
LRG_216p1:p.Leu73Arg
NC_000003.11:g.37042456T>G
NM_000249.3:c.218T>G

Protein change:

L73R; LEU73ARG

Links:

OMIM: 120436.0034; dbSNP: rs397514684

NCBI 1000 Genomes Browser:

rs397514684

Molecular consequence:

NM_001167617.3:c.-72T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167618.3:c.-506T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167619.3:c.-414T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258273.2:c.-506T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258274.3:c.-506T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354615.2:c.-409T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354616.2:c.-414T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354617.2:c.-506T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354618.2:c.-506T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354619.2:c.-506T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354620.2:c.-72T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354621.2:c.-599T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354622.2:c.-712T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354623.2:c.-712T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354624.2:c.-609T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354625.2:c.-512T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354626.2:c.-609T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354627.2:c.-609T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354629.2:c.208-3436T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000249.4:c.218T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001258271.2:c.218T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354628.2:c.218T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354630.2:c.218T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Mismatch repair cancer syndrome 1 (MMRCS1)
Synonyms:: BRAIN TUMOR-POLYPOSIS SYNDROME 1; BTP1 SYNDROME; CHILDHOOD CANCER SYNDROME; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010159; MedGen: C5399763; Orphanet: 252202; OMIM: 276300

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Mus musculus acetyl-Coenzyme A acyltransferase 2 (mitochondrial 3-oxoacyl-Coenzy...
Mus musculus acetyl-Coenzyme A acyltransferase 2 (mitochondrial 3-oxoacyl-Coenzyme A thiolase) (Acaa2), mRNA
gi|29126204|ref|NM_177470.1|

Nucleotide
Homo sapiens sphingomyelin synthase 2 (SGMS2), mRNA
Homo sapiens sphingomyelin synthase 2 (SGMS2), mRNA
gi|37059795|ref|NM_152621.3|

Nucleotide
LOC128191775 [Magallana angulata]
LOC128191775 [Magallana angulata]
Gene ID:128191775

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000058656	OMIM	no assertion criteria provided	Pathogenic (Jan 1, 2013)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000058656

OMIM

no assertion criteria provided

Pathogenic
(Jan 1, 2013)

germline

literature only

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	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Agenesis of the corpus callosum and gray matter heterotopia in three patients with constitutional mismatch repair deficiency syndrome.

Baas AF, Gabbett M, Rimac M, Kansikas M, Raphael M, Nievelstein RA, Nicholls W, Offerhaus J, Bodmer D, Wernstedt A, Krabichler B, Strasser U, Nyström M, Zschocke J, Robertson SP, van Haelst MM, Wimmer K.

Eur J Hum Genet. 2013 Jan;21(1):55-61. doi: 10.1038/ejhg.2012.117. Epub 2012 Jun 13.

PubMed [citation]

PMID:: 22692065
PMCID:: PMC3522206

Details of each submission

From OMIM, SCV000058656.5

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

Description

In a boy (patient 2) with mismatch repair cancer syndrome (MMRCS1; 276300), Baas et al. (2013) identified a homozygous c.218T-G transversion in exon 3 of the MLH1 gene, resulting in a leu73-to-arg (L73R) substitution. His parents were unrelated, but originated from the same Polynesian Pacific Island population. In vitro functional expression studies showed that the mutant protein had no DNA repair activity. The patient first presented with a glioblastoma multiforme and later developed a T-cell lymphoblastic lymphoma. He died of sepsis at the end of treatment. Brain imaging showed near complete agenesis of the corpus callosum, interhemispheric and intracerebral cysts, and right subcortical and periventricular heterotopia. He was also noted to have multiple cafe-au-lait spots. The maternal family history was positive for colorectal cancer.

#	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

Last Updated: Oct 26, 2024

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