Description
This variant is denoted MSH2 c.2354A>C at the cDNA level, p.His785Pro (H785P) at the protein level, and results in the change of a Histidine to a Proline (CAT>CCT). This variant has been identified in at least one individual with a personal and family history of colorectal cancer, co-occurring with a POLD1 variant (Chubb 2015). MSH2 His785Pro was not observed at a significant allele frequency in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Histidine and Proline differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. MSH2 His785Pro occurs at a position that is conserved across species and is located in the ATPase domain (Lützen 2008, Kansikas 2011). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether MSH2 His785Pro is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
# | Sample | Method | Observation |
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Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
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1 | germline | yes | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |