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MLH1 V384D
GeneMLH1
Variantmissense
Amino Acid ChangeV384D
Transcript ID (GRCh37/hg19)ENST00000231790
Codon384
Exon12
Germline/Somatic?Somatic
Pertinent Negative In
Tumor TypePrimary Site
See All Pertinent Negatives

Interpretations

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Tier 3
MLH1
Variants
MLH1 V384D
Primary Sites
Lung
Colon
Rectum
Tumor Types
Adenocarcinoma
Carcinoma
Interpretation

The MLH1 V384D polymorphism has been associated with cancer risk in some tumor types. In addition, according to one report, MLH1 V384D polymorphism has been reported to be associated with primary resistance to EGFR-TKIs in patients with EGFR L858R-positive lung adenocarcinoma and may potentially be a novel biomarker to guide treatment decisions for those patients. The effect of this MLH1 polymorphism when present with other EGFR-TKI sensitizing mutations such as Exon 19 deletions in EGFR remains to be clarified. Some studies have shown that patients carrying the MLH1 V384D variant have an increased risk of the development of microsatellite-instable as well as -stable colorectal cancer. This variant has an allele frequency of 4% in the East Asian population. Of note, this variant is reported as a benign germline variant in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/41632/). Clinical correlation is recommended.

Last updated: 2018-05-09 21:13:25 UTC
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Tier 3
MLH1
Variants
MLH1 V384D
Primary Sites
Thyroid
Tumor Types
Papillary Carcinoma
Interpretation

MLH1 is a component of the cellular DNA mismatch repair (MMR) machinery causing hereditary nonpolyposis colorectal cancer (HNPCC), and is associated with specific somatic alterations in the tumor, characterized by high microsatellite instability (MSI-H). The MLH1 V384D mutation has been associated with cancer risk in some tumor types. This variant encodes in a partially impaired protein with diminished interaction with PMS2 protein and reduced MMR activity in vitro. The MLH1 V384D variant has not been reported in thyroid tumors. However, some other MLH1 variants have been described in some thyroid tumors, but their clinical significance is yet to be determined. Of note, according to one report, MLH1 V384D variant has been reported to be associated with primary resistance to EGFR-TKIs in patients with EGFR L858R-positive lung adenocarcinoma. Clinical correlation is recommended.

Last updated: 2017-01-30 21:13:28 UTC
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Tier 3
MLH1
Variants
MLH1 V384D
Primary Sites
Brain
Tumor Types
Glioblastoma
Astrocytoma, NOS
Astrocytoma, Pilocytic
Astrocytoma, Diffusely Infiltrating
Interpretation

MLH1 is a component of the cellular DNA mismatch repair (MMR) machinery. The MLH1 V384D mutation has been associated with cancer risk in some tumor types. This variant encodes in a partially impaired protein with diminished interaction with PMS2 protein and reduced MMR activity in vitro. The MLH1 V384D variant has not been reported as a somatic mutation in glial brain tumors. This variant has an allele frequency of 4% in the East Asian population. Some studies have shown that patients carrying the MLH V384D variant have an increased risk of the development of microsatellite-instable as well as -stable colorectal cancer. MLH1 V384D variant has also been reported to be associated with primary resistance to EGFR-TKIs in patients with EGFR L858R-positive lung adenocarcinoma. Of note, this variant is reported as a benign germline variant in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/41632/). Clinical correlation is recommended.

Last updated: 2018-04-25 15:38:14 UTC
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When using PMKB, please cite: Huang et al., JAMIA 2017


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