Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000219544 | SCV000275686 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-05-08 | criteria provided, single submitter | clinical testing | Insufficient or conflicting evidence |
| Color | RCV000219544 | SCV000904822 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-11-23 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001204480 | SCV001375687 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2019-06-03 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with serine at codon 160 of the MLH1 protein (p.Ala160Ser). The alanine residue is weakly conserved and there is a moderate physicochemical difference between alanine and serine. 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 conditions. ClinVar contains an entry for this variant (Variation ID: 231743). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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. |