Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000195588 | SCV000254374 | uncertain significance | Lynch syndrome | 2015-04-28 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with alanine at codon 307 of the MLH1 protein (p.Val307Ala). The valine residue is highly conserved and there is a small physicochemical difference between valine and alanine. This variant has not been published in the literature and is not present in population databases. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. In summary, this is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV002372188 | SCV002688136 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-02 | criteria provided, single submitter | clinical testing | The p.V307A variant (also known as c.920T>C), located in coding exon 11 of the MLH1 gene, results from a T to C substitution at nucleotide position 920. The valine at codon 307 is replaced by alanine, 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. |