Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001048486 | SCV001212495 | uncertain significance | Arrhythmogenic right ventricular dysplasia 13 | 2020-11-17 | 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Not available"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with CTNNA3-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with threonine at codon 847 of the CTNNA3 protein (p.Met847Thr). The methionine residue is moderately conserved and there is a moderate physicochemical difference between methionine and threonine. |
Ambry Genetics | RCV003160376 | SCV003911603 | uncertain significance | Inborn genetic diseases | 2023-02-16 | criteria provided, single submitter | clinical testing | The p.M847T variant (also known as c.2540T>C), located in coding exon 17 of the CTNNA3 gene, results from a T to C substitution at nucleotide position 2540. The methionine at codon 847 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |