Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000199190 | SCV000254373 | uncertain significance | Lynch syndrome | 2015-04-30 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with lysine at codon 30 of the MLH1 protein (p.Asn30Lys). The asparagine residue is highly conserved and there is a moderate physicochemical difference between asparagine and lysine. 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 | RCV002372187 | SCV002684742 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-12-29 | criteria provided, single submitter | clinical testing | The p.N30K variant (also known as c.90T>G), located in coding exon 1 of the MLH1 gene, results from a T to G substitution at nucleotide position 90. The asparagine at codon 30 is replaced by lysine, an amino acid with similar properties. This amino acid position is highly 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. |