Personalized Interpretation and Clinical Translation of Genetic Variants Associated With Cardiomyopathies

FIGURE 1. Electropherogram of pathogenic variants identified in our families and closest proteins interactions. (A) Families A and B: c.275T > A (TTG > TAG), p.L92X (p.Leu92∗) in the PKP2 gene. Families C and D: c.1237C > T (CGA > TGA) and p.R413X (p.Arg413∗) in the PKP2 gene. Families E and F: c.2670dupG, p.R891A_frX160 (p.Arg891Ala_fs∗160) in the MYBPC3 gene. (B) Network of ten closest proteins to PKP2. (C) Network of ten closest proteins to MYBPC3.

FIGURE 2. Pedigree of family (A). Generations are indicated in the left side. Each individual is identified with a number. Clinically affected patients are show in gray, clinically unaffected patients are show in white, and slashes indicate a deceased relative. Index case is indicated with an arrow (III.1). The genetic carriers of PKP2_p.(Leu92∗) are represented with a plus sign inside rounds/squares. Minus sign indicates non-carriers of the genetic variant. Question mark indicates no genetic analysis available. The ECG corresponds to index case. The ECG showing negative T waves in V1-3, and prolonged Terminal Activation Duration as major and respectively, minor diagnostic Task Force Criteria for ACM.

FIGURE 3. Pedigree of family B. Generations are indicated in the left side. Each individual is identified with a number. Clinically affected patients are shown in gray, clinically unaffected patients are shown in white, and slashes indicate a deceased relative. Index case is indicated with an arrow (III.1). The genetic carriers of PKP2_p.(Leu92∗) are represented with a plus sign inside rounds/squares. Minus sign indicates non-carriers of the genetic variant. Question mark indicates no genetic analysis available. SD means Sudden Death. The ECG corresponds to index case. ECG showing negative T waves in V1-2 (minor ACM criterion).

FIGURE 4. Pedigree of family C. Generations are indicated in the left side. Each individual is identified with a number. Clinically affected patients are shown in gray, clinically unaffected patients are shown in white, and slashes indicate a deceased relative. Index case is indicated with an arrow (II.2). The genetic carriers of PKP2_p.(Arg413∗) are represented with a plus sign inside rounds/squares. Minus sign indicates non-carriers of the genetic variant. Question mark indicates no genetic analysis available. SD means Sudden Death. The ECG corresponds to index case.

FIGURE 5. Pedigree of family D. Generations are indicated in the left side. Each individual is identified with a number. Clinically affected patients are shown in gray, clinically unaffected patients are shown in white, and slashes indicate a deceased relative. Index case is indicated with an arrow (IV.1). The genetic carriers of PKP2_p.(Arg413∗) are represented with a plus sign inside rounds/squares. Minus sign indicates non-carriers of the genetic variant. Question mark indicates no genetic analysis available. SD means Sudden Death. The ECG corresponds to IV.1.

FIGURE 6. Pedigree of family E. Generations are indicated in the left side. Each individual is identified with a number. Clinically affected patients are shown in gray, clinically unaffected patients are shown in white, and slashes indicate a deceased relative. Index case is indicated with an arrow (III.2). The genetic carriers of MYBPC3_p.(Arg891Alafs∗160) are represented with a plus sign inside rounds/squares. Minus sign indicates non-carriers of the genetic variant. Question mark indicates no genetic analysis available. SD means Sudden Death. The ECG corresponds to index case.

FIGURE 7. Pedigree of family F. Generations are indicated in the left side. Each individual is identified with a number. Clinically affected patients are shown in gray, clinically unaffected patients are shown in white, and slashes indicate a deceased relative. Index case is indicated with an arrow (II.2). The genetic carriers of MYBPC3_p.(Arg891Alafs∗160) are represented with a plus sign inside rounds/squares. Minus sign indicates non-carriers of the genetic variant. Question mark indicates no genetic analysis available. The ECG corresponds to index case.