Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color | RCV000579430 | SCV000684809 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-08-26 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000822650 | SCV000963460 | uncertain significance | Hereditary nonpolyposis colon cancer | 2018-08-10 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with tryptophan at codon 9 of the MLH1 protein (p.Arg9Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with colorectal cancer and adenomatous polyposis (PMID: 22736432). However, in this individual a pathogenic mutation was also identified in APC, which suggests that this c.25C>T variant was not the primary cause of disease. ClinVar contains an entry for this variant (Variation ID: 90122). Experimental studies have shown that this missense change (p.Arg9Trp) partially reduced the DNA mismatch repair activity and produced significantly lower amount of MLH1 protein compared to the wild-type protein (PMID: 22736432). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |