Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002415338 | SCV002721178 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-04 | criteria provided, single submitter | clinical testing | The p.L628V variant (also known as c.1882T>G), located in coding exon 16 of the MLH1 gene, results from a T to G substitution at nucleotide position 1882. The leucine at codon 628 is replaced by valine, 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, |
RCV004007376 | SCV004830384 | uncertain significance | Lynch syndrome | 2023-08-28 | criteria provided, single submitter | clinical testing | This missense variant replaces leucine with valine at codon 628 of the MLH1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 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 not been identified 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. |