Author`s Reply.

To the Editor,

We are delighted with the interest shown in our work.

In our article published in the Anatolia Journal of Cardiology in late 2016 entitled “A hypertrophic and dilated cardiomyopathic sudden cardiac death case; de novo mutations TTN and SGCD genes”, we demonstrated that the likely benign [NM_000337.5(SGCD):c.15G>C: (p.Glu5Asp)] and the missense [NM_003319.4(TTN):c.21758T>C (Ile7253Thr)] variants could be associated with dilated cardiomyopathy (DCM)/hypertrophic cardiomyopathy (HCM) as a (cor bovinum) disease or in young sudden cardiac death (1).

In the letter to the editor, it was claimed that our variant (TTN):c.21758T>C had been previously identified by Pugh et al. (2) and that therefore, the variant is no longer novel. However, this is immaterial because there is no such variant (TTN):c.21758T>C reported by Pugh et al. (2) (see Suplementary-1 Cases).

Although the genes NM_000337.5(SGCD):c.15G>C (p.Glu5Asp) and NM_003319.4(TTN):c.21758T>C (Ile7253Thr) were identified as likely benign and missense variants, respectively, in National Center for Biotechnology Information (NCBI) database and had not been previously reported as disease or death-causing variants, we found that titin (TTN) and sarcoglycan (SGCD) genes are associated with HCM/DCM and DCM, since cause of death was determined to be sudden circulatory failure resulting from DCM/HCM.

We used the term “de novo” in our case report to mean a new instance, and perhaps were not attentive enough to its very specific genetic nomenclature. Regarding the comments on SGCD variant of “unknown significance,” there are many ins- tances of single point mutations causing serious disease (e.g., sickle cell anemia). While we cannot definitively conclude that the mutation caused the heart pathology, we believe it is important to report this and similar cases, as these are relevant to whether these variants could merit further study. We agree that larger cardiologic clinical studies and sophisticated genetic studies carried out by specialists are required to clarify these issues. However, this lies outside the scope of the current work.