Reevaluating the Mutation Classification in Genetic Studies of Bradycardia Using ACMGAMP Variant Classification Framework

الملخص EN

Purpose.

Next-generation sequencing (NGS) has become more accessible, leading to an increasing number of genetic studies of familial bradycardia being reported.

However, most of the variants lack full evaluation.

The relationship between genetic factors and bradycardia should be summarized and reevaluated.

Methods.

We summarized genetic studies published in the PubMed database from 2008/1/1 to 2019/9/1 and used the ACMG/AMP classification framework to analyze related sequence variants.

Results.

We identified 88 articles, 99 sequence variants, and 34 genes after searching the PubMed database and classified ABCC9, ACTN2, CACNA1C, DES, HCN4, KCNQ1, KCNH2, LMNA, MECP2, LAMP2, NPPA, SCN5A, and TRPM4 as high-priority genes causing familial bradycardia.

Most mutated genes have been reported as having multiple clinical manifestations.

Conclusions.

For patients with familial CCD, 13 high-priority genes are recommended for evaluation.

For genetic studies, variants should be carefully evaluated using the ACMG/AMP variant classification framework before publication.