Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000222167 | SCV000276766 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-10-10 | criteria provided, single submitter | clinical testing | The p.K196T variant (also known as c.587A>C), located in coding exon 7 of the MLH1 gene, results from an A to C substitution at nucleotide position 587. The lysine at codon 196 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Color Diagnostics, |
RCV000222167 | SCV000689896 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-17 | criteria provided, single submitter | clinical testing | This missense variant replaces lysine with threonine at codon 196 of the MLH1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MLH1-related disorders in the literature. This variant has been identified in 1/31408 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Labcorp Genetics |
RCV000630034 | SCV000750990 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2025-01-01 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001550623 | SCV001770978 | uncertain significance | not provided | 2024-10-03 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 22753075) |