Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001211280 | SCV001382811 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2019-10-01 | criteria provided, single submitter | clinical testing | 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. 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: "Benign"; Align-GVGD: "Class C25"). This variant has not been reported in the literature in individuals with MSH2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with threonine at codon 927 of the MSH2 protein (p.Ile927Thr). The isoleucine residue is weakly conserved and there is a moderate physicochemical difference between isoleucine and threonine. |
Ambry Genetics | RCV002436814 | SCV002751686 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-11-01 | criteria provided, single submitter | clinical testing | The p.I927T variant (also known as c.2780T>C), located in coding exon 16 of the MSH2 gene, results from a T to C substitution at nucleotide position 2780. The isoleucine at codon 927 is replaced by threonine, an amino acid with similar properties. This amino acid position is well 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. |