Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001238286 | SCV001411089 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2021-12-22 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 964127). This variant has not been reported in the literature in individuals affected with MLH1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 195 of the MLH1 protein (p.Lys195Glu). |
Ambry Genetics | RCV002357019 | SCV002650840 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-07-31 | criteria provided, single submitter | clinical testing | The p.K195E variant (also known as c.583A>G), located in coding exon 7 of the MLH1 gene, results from an A to G substitution at nucleotide position 583. The lysine at codon 195 is replaced by glutamic acid, 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. |