Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV001184938 | SCV001351036 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-12-16 | criteria provided, single submitter | clinical testing | This variant replaces alanine with valine at codon 125 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).Splice site prediction tools suggest that this variant may activate a cryptic donor site. However, this prediction has not been confirmed in published RNA studies. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer 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. |