R226L (p.Arg226Leu) variant of MLH1 (DNA mismatch repair protein Mlh1)
R226L (p.Arg226Leu) in MLH1 (DNA mismatch repair protein Mlh1) is a missense change. Clinical records from ClinVar, EBI, and UniProt describe it as likely pathogenic in the context of Lynch syndrome. The available variant effect predictions contribute to a CATVariant prioritization score of 0.90 / 1. The record also includes population frequency data, published literature, and structural context.
R226L (p.Arg226Leu) variant details
- p.Arg226Leu
- rs63751711
- ClinGen CA011592
- ClinVar RCV000075810
- ClinVar RCV000160555
- Likely pathogenic
- Lynch syndrome
- Missense
- Variant Prioritization Score for Impact Estimate 0.903
- REVEL 0.90
- ESM-1b 1.00
- AlphaMissense 0.82
- MetaLR 0.87
- MetaSVM 0.90
- CADD 42.00
- ClinVar: Likely pathogenic (Lynch syndrome)
- EBI: Pathogenic (in LYNCH2)
- UniProt: Pathogenic (in LYNCH2)
- Most common in the 1KG:CEU population (allele frequency 0.0042)
- Structural context available
- Cited in: CpG dinucleotides in the hMSH2 and hMLH1 genes are hotspots for HNPCC mutations. (PMID 8566964)
- Cited in: Practice parameters for the identification and testing of patients at risk for dominantly inherited colorectal… (PMID 11598466)