Description
The MSH6 p.Val800Leu variant was identified in 1 of 558 proband chromosomes (frequency 0.002) from individuals with colorectal cancer (Kim 2004, Kolodner 1999) and was identified in 1 of 1038 control chromosomes (frequency 0.001) from these studies, increasing the likelihood that this may be a low frequency polymorphism. This variant was also identified in dbSNP (ID# rs61748083) “with untested allele”, in the Exome Variant Server ESP Project with a frequency of 0.0002 in European American alleles, and in the HGMD, MutDB, MMR DB, and InSIGHT Colon Cancer databases. The p.Val800 residue is not conserved in mammals and lower organisms, and computational analyses (PolyPhen2, SIFT, AlignGVGD, BLOSUM) do not suggest a high likelihood of impact to the protein. In addition, two in silico studies which assessed the impact of the variant on protein structure and function predicted this variant was neutral (Ali 2012, Terui 2013). However, this information is not predictive enough to rule out pathogenicity. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as predicted benign.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | unknown | yes | not provided | not provided | not provided | | 1 | not provided | not provided | not provided |
