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. 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. 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.

中文翻译：

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伊朗人群中MYH7基因错义变异的预测和计算机验证：基于Iranome数据库的生物信息学分析

识别特定人群中的致病遗传变异可改善遗传疾病的分子诊断。国家基因组数据库提供了有关此事的宝贵信息。本研究旨在调查与常见心脏病（即遗传性心肌病）相关的 MYH7 基因的基因组变异。从Iranome数据库中提取MYH7基因变异并加载到SPSS软件中。过滤步骤是根据变体规范执行的，重点是识别错义变化。使用预测算法，研究了等位基因频率和功能缺陷等变化的不同方面。我们的结果表明，与 18 个 (7.7%) 错义改变相比，41 个 (17.4%) 编码变体是同义词。错义变体主要在编码 MyHC α-螺旋杆尾的外显子 20-40 中观察到。已知 p.Pro211Leu、p.Arg787His、p.Val964Leu、p.Arg1277Gln 和 p.Ala1603Thr 与遗传性心肌病有关。四个错义变体，p.Asn1623Ser、p.Arg1588His、p.Phe1498Tyr 和 p.Arg1129Ser，位于 MyHC α-螺旋杆尾，并且它们都没有在 dbSNP 或 genomAD 数据库上注释。我们的研究显示了伊朗人群中与该疾病相关的几种 MYH7 变异。结果强调了分析编码 MyHC α-螺旋杆尾的外显子的重要性。基因组数据库的调查可以被认为是一种使用靶向突变检测分析的具有成本效益的策略。这种预测方法的有效性应该在对患者队列的进一步研究中得到阐明。