NM_000249.3(MLH1):c.218T>G (p.Leu73Arg) AND Turcot syndrome

Clinical significance:Pathogenic (Last evaluated: Jan 1, 2013)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000035016.26

Allele description [Variation Report for NM_000249.3(MLH1):c.218T>G (p.Leu73Arg)]

NM_000249.3(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_000249.3(MLH1):c.218T>G (p.Leu73Arg)
HGVS:
  • NC_000003.12:g.37000965T>G
  • NG_007109.2:g.12616T>G
  • NM_000249.3:c.218T>G
  • NM_001167617.1:c.-72T>G
  • NP_000240.1:p.Leu73Arg
  • LRG_216t1:c.218T>G
  • LRG_216:g.12616T>G
  • LRG_216p1:p.Leu73Arg
  • NC_000003.11:g.37042456T>G
Protein change:
L73R; LEU73ARG
Links:
OMIM: 120436.0034; dbSNP: 397514684
NCBI 1000 Genomes Browser:
rs397514684
Molecular consequence:
  • NM_001167617.1:c.-72T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_000249.3:c.218T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Turcot syndrome (MMRCS)
Synonyms:
MISMATCH REPAIR CANCER SYNDROME; BRAIN TUMOR-POLYPOSIS SYNDROME 1; BTP1 SYNDROME; See all synonyms [MedGen]
Identifiers:
MedGen: C0265325; Orphanet: 252202; OMIM: 276300

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000058656OMIMno assertion criteria providedPathogenic
(Jan 1, 2013)
germlineliterature only

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature 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, SCV000058656.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In a boy with mismatch repair cancer syndrome (MMRCS; 276300), Baas et al. (2013) identified a homozygous 218T-to-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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Apr 27, 2018