Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000801126 | SCV000940890 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2023-09-19 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 232 of the MLH1 protein (p.Gly232Val). This variant is present in population databases (rs149302013, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with MLH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 646770). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |
| Ambry Genetics | RCV001025846 | SCV001188111 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-07-03 | criteria provided, single submitter | clinical testing | The p.G232V variant (also known as c.695G>T), located in coding exon 9 of the MLH1 gene, results from a G to T substitution at nucleotide position 695. The glycine at codon 232 is replaced by valine, an amino acid with dissimilar properties. This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration may weaken the native splice acceptor site; however, direct evidence is insufficient at this time (Ambry internal data). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this amino acid alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001800887 | SCV002046858 | uncertain significance | not provided | 2021-04-14 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV004569576 | SCV005058014 | uncertain significance | Colorectal cancer, hereditary nonpolyposis, type 2 | 2023-12-15 | criteria provided, single submitter | clinical testing |