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

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

Variant type:
single nucleotide variant
Cytogenetic location:
3p22
Genomic location:
  • Chr3:37042456 (on Assembly GRCh37)
  • Chr3:37000965 (on Assembly GRCh38)
Protein change:
L73R
HGVS:
  • NG_007109.2:g.12616T>G
  • NM_000249.3:c.218T>G
  • NC_000003.12:g.37000965T>G
  • NC_000003.11:g.37042456T>G
  • NP_000240.1:p.Leu73Arg
  • LRG_216p1:p.Leu73Arg
  • LRG_216t1:c.218T>G
  • LRG_216:g.12616T>G
Links:
NCBI 1000 Genomes Browser:
rs397514684
Molecular consequence:
  • NM_000249.3:c.218T>G: missense variant SO:0001583
  • NM_001167617.1:c.-72T>G: 5 prime UTR variant SO:0001623

Clinical significance

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

Clinical significance:
Pathogenic/Likely pathogenic
Review status:
(1/4)1 star out of maximum of 4 stars
classified by single submitter
Number of submission(s):
1
Condition(s)
See supporting ClinVar records

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Assertion and evidence details

Germline

Clinical significance
(Last evaluated)
Review status
(Assertion method)
Collection methodCondition(s)
(Mode of inheritance)
OriginCitationsSubmitter
(Last submitted)
Submission accession
Pathogenic
(May 1, 2013)
classified by single submitter
(literature only)
literature onlygermlinePubMed (1)
OMIM
(Apr 29, 2013)
SCV000058656

Summary

FamiliesIndividualsSegregationAllele originEthnicityGeographic origin
not providednot providednot providedgermlinenot providednot provided

OMIM

Data published from literature

FamiliesIndividualsSegregationsAllele originCitations
not providednot providednot providedgermline

Description

In a boy with mismatch repair cancer syndrome (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.

Last Updated: Nov 22, 2014

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