Prediction and in silico validation of MYH7 gene missense variants in the Iranian population: a bioinformatics analysis based on Iranome database

Abstract

Abstract Background Identifying disease-causing genetic variants in a particular population improves the molecular diagnosis of genetic disorders. National genome databases provide valuable information on this matter. This study aimed to investigate the genomic variants of the MYH7 gene, related to the common heart disease, i.e., hereditary cardiomyopathy. Results MYH7 gene variants were extracted from the Iranome database and loaded into SPSS software. The filtration steps were performed based on the variant specification and with emphasis on identifying missense changes. Using predictive algorithms, different aspects of the changes such as allele frequency and functional defects were investigated. Our results showed that 41 (17.4%) coding variants were synonymous compared with 18 (7.7%) missense alterations. The missense variants were mostly observed in exons 20–40 that encode MyHC α-helical rod tail. The p.Pro211Leu, p.Arg787His, p.Val964Leu, p.Arg1277Gln, and p.Ala1603Thr were already known to be associated with inherited cardiomyopathy. Four of the missense variants, p.Asn1623Ser, p.Arg1588His, p.Phe1498Tyr, and p.Arg1129Ser, were located on MyHC α-helical rod tail and none of them was annotated on dbSNP or genomAD databases. Conclusion Our study showed several MYH7 variants associated with the disease in the Iranian population. The results emphasize the importance of analyzing the exons encoding MyHC α-helical rod tail. The investigation of genomic databases can be considered as a cost-effective strategy using targeted mutation detection analyses. The efficacy of this prediction method should be elucidated in further studies on patients’ cohorts.