Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000544189 | SCV000625055 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2022-03-26 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with MLH1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 430 of the MLH1 protein (p.Glu430Gln). ClinVar contains an entry for this variant (Variation ID: 455383). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MLH1 protein function. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001800733 | SCV002046551 | uncertain significance | not provided | 2021-01-02 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002384036 | SCV002690174 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-09 | criteria provided, single submitter | clinical testing | The p.E430Q variant (also known as c.1288G>C), located in coding exon 12 of the MLH1 gene, results from a G to C substitution at nucleotide position 1288. The glutamic acid at codon 430 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| All of Us Research Program, |
RCV004003710 | SCV004822008 | uncertain significance | Lynch syndrome | 2023-08-15 | criteria provided, single submitter | clinical testing |