ClinVar

Description

This sequence change deletes 3 nucleotides from exon 4 of the MSH6 mRNA (c.2561_2563delAGA). This leads to the deletion of 1 amino acid residue in the MSH6 protein (p.Lys854del) but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs751683437, ExAC 0.003%). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with constitutional mismatch repair deficiency syndrome (PMID: 26318770). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 142970). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acid is currently unknown. In summary, this is a rare in-frame deletion of 1 amino acid residue with uncertain impact on protein function. It has been reported in the population and an affected individual, but the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.