Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000472080 | SCV000548152 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2021-08-28 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with alanine at codon 552 of the MSH2 protein (p.Thr552Ala). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and alanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with MSH2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
Ambry Genetics | RCV002402257 | SCV002707075 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-02-03 | criteria provided, single submitter | clinical testing | The p.T552A variant (also known as c.1654A>G), located in coding exon 10 of the MSH2 gene, results from an A to G substitution at nucleotide position 1654. The threonine at codon 552 is replaced by alanine, an amino acid with similar properties. This amino acid position is well 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. |
All of Us Research Program, |
RCV004000778 | SCV004842959 | uncertain significance | Lynch syndrome | 2023-11-30 | criteria provided, single submitter | clinical testing |