Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002433298 | SCV002742945 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-11-06 | criteria provided, single submitter | clinical testing | The p.L85R variant (also known as c.254T>G), located in coding exon 3 of the MLH1 gene, results from a T to G substitution at nucleotide position 254. The leucine at codon 85 is replaced by arginine, an amino acid with dissimilar 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. In addition, this alteration is predicted to be deleterious by MAPP-MMR in silico analyses (Chao EC et al. Hum. Mutat. 2008 Jun;29:852-60). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
All of Us Research Program, |
RCV004007435 | SCV004835262 | uncertain significance | Lynch syndrome | 2023-12-13 | criteria provided, single submitter | clinical testing | This missense variant replaces leucine with arginine at codon 85 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 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. |