Associated disorders

The MLH1 gene is associated with autosomal dominant Lynch syndrome (also called hereditary nonpolyposis colorectal cancer syndrome, or HNPCC) (MedGen UID: 232603) and autosomal recessive constitutional mismatch repair deficiency syndrome (CMMR-D) (MedGen UID: 78553).

MLH1 is a member of a group of DNA mismatch repair (MMR) genes, which encode proteins that detect and repair DNA mismatches that can occur during cell replication. The MLH1 and PMS2 gene products interact via their C-terminal domains to form a protein complex. This complex coordinates the activities of other proteins that repair mistakes made during DNA replication. Loss of MLH1 function due to pathogenic variants causes defective DNA mismatch repair, leading to accumulation of errors in the DNA sequence as cells continue to divide, thereby increasing the risk of tumor formation.

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
MLH1* NM_000249.3

*MLH1: Deletion/duplication analysis covers the promoter region.