Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001361508 | SCV001557484 | uncertain significance | Arrhythmogenic right ventricular dysplasia 13 | 2020-09-13 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with CTNNA3-related conditions. 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 tyrosine 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 is present in population databases (rs141141746, ExAC 0.001%). This sequence change replaces histidine with tyrosine at codon 643 of the CTNNA3 protein (p.His643Tyr). The histidine residue is moderately conserved and there is a moderate physicochemical difference between histidine and tyrosine. |