Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000697461 | SCV000826073 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2019-11-20 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine with arginine at codon 318 of the MLH1 protein (p.His318Arg). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MLH1-related disease. ClinVar contains an entry for this variant (Variation ID: 575285). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |
| Color | RCV000771670 | SCV000904294 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-06-05 | criteria provided, single submitter | clinical testing |