L-Type Calcium Channel: Predicting Pathogenic/Likely Pathogenic Status for Variants of Uncertain Clinical Significance

Round 1

Reviewer 1 Report

The article by Tarnovskaya et al investigated various computational tools via their application to V-gated sodium & calcium channels in order to characterize or predict the 'pathogenicity' status of the channel.

The study reveals some fundamental insights into which kind of channel variants were more susceptible to being pathogenic. Also the application of various bioinformatics tools allowed some benchmark results in terms of the performance of classifying the pathogenic variants from benign ones.

The findings from this study will allow better diagnostics of health conditions especially heart conditions and is indeed quite useful to study furthermore.

This work should be read by a wider scientific audience.

Author Response

Response to Reviewer 1

Comment 1: Moderate English changes required

Response 1: Grammar errors in the manuscript are fixed.

Comment 2: The introduction and the results can be improved.

Response 2:  We added some clarifications to the introduction and results. We hope that these changes will improve the understanding of the text.

Reviewer 2 Report

The manuscript by Svetlana et al describes the potential of single mutations of  voltage gated sodium and calcium channels that might potentially lead to disease. 

the experimental designs, and results are fully explained. 

But there are obvious grammer errors and awkward sentences in the text, which means author should edit the text very throughly. there are errors in the figure titles and captions as well. 

Author Response

Response to Reviewer 2

Comment 1: Moderate English changes required

Response 1: Grammar errors are fixed

Comment 2: The research design can be improved.

Response 2: We added some clarification to the section “Materials and Methods”.

Round 2

Reviewer 2 Report

The authors addressed my points properly.