Mutation | Cell line | Peak force | T1 | T2 | Cell size | Disarray | Multinucleation | Other phenotypes | Reference |
---|---|---|---|---|---|---|---|---|---|
MYH7 Het p.Arg663His | Patient | NA | NA | NA |  + 60% |  + 250% | 50% vs. 20% | Increased normalized contractile motion, elevated [Ca2+]i, decreased Ca2+ release, increased DAD | [79] |
MYBPC3 Het Gly999-Gln1004del | Patient | NA | NA | NA |  + 20% |  + 50% | NA | cMyBPC–20% | [153] |
MYBPC3 Het Exon 25 | Patient | NA | NA | NA |  + 50 − 100% | NA | NA | NA | [154] |
MYH7 Het p.Arg442Gly | Patient | NA | NA | NA |  + 15% |  + 150% | NA | Resting [Ca2+]i + 20%, decreased Ca2+ store, APD prolongation + 60%, arrhythmias + 300%, ICa and INa up | [155] |
MYBPC3 Het c.2373dupG | Patient |  − 50% | NA | NA | ± | NA | NA | cMyBPC haploinsufficiency | [156] |
TPM1 Het p.Asp175Asn MYBPC3 Het p.Gln1061X | Patient | NA | NA | NA | ± (T);  + 100% (M) | NA | 40% vs. 20% (T); 45% vs. 20% (M) | Prolonged APD, increased arrhythmias (T, not M), increased DAD (M, not T), TPM1 up in T, MYBPC3 up in M | [157] |
MYH7 Het p.Glu848Gly | Patient |  − 50% | NA | NA |  + 40% | Yes, but not quantified | NA | Increased Ca2+ sensitivity, KAct + 60% | [158] |
MYH7 Het p.Val698Al | Patient | NA | NA | NA | NA | NA | NA | NA | [159] |
MYBPC3 Het c.1358-1359insC | Patient | NA | NA | NA |  + 65% | NA | NA | cMyBPC haploinsufficiency | [160] |
TNNT2 Het c.236 T > A | Isogenic | NA | NA | NA | NA | NA | NA | Increased Ca2+ sensitivity, decreased peak Ca2+ transients, APD50 prolongation + 70% | [161] |
MYBPC3 Het Δ25/ p.Asp389Val | Patient | NA | NA | NA |  + 100% | NA | NA | Ca2+ transient irregularities + 500% | [162] |
MT-RNR2 Het m.2336 T > C | Patient | NA | NA | NA |  + 27% | No | NA | [Ca2+]i + 60%, increased SR store, ICa − 43%, APD prolongation + 14%, increased DAD, mitochondrial 16S rRNA − 55%, MMP − 25%, ATP/ADP ratio − 53%; | [163] |
MYL3 Het c.170C > G MYBPC3 Het p.Val321Met | Patient and isogenic | NA | NA | NA | ± | No | NA | Increased diastolic [Ca2+]i, DAD, contraction and relaxation (in MYL3, not MYBPC3) velocity slightly up | [164] |
TNNT2 Het p.Ile79Asn | Patient | NA |  + 75% |  + 30% | ± |  + 60% | NA | Decreased sarcomere length, increased Ca2+ sensitivity, higher Ca2 + buffering, decreased peak Ca2+ transients, shortened early repolarization | [165] |
MYH7 Het/Hom c.C9123T | Isogenic |  − 20% (Het); − 70% (Hom) |  + 20% | ± |  + 50% | Yes | 2% vs. 1% | Increased DAD, basal and maximal respiration up, increased ATP production, MYH7/MYH6 ratio up | [166] |
TPM1 Het p.Asp175Asn MYBPC3 Het p.Gln1061X | Patient | NA | NA | NA | NA | NA | NA | Decreased ICa, increased Ito and IK1, increased DAD and EAD | [167] |
MYH7 Het p.Arg723Cys; MYH7 Het p.Arg403Gln; MYH7 Het p.Arg663His; MYBPC3 Het p.Arg943x; TNNI3 Het p.Arg186Gln | Patient | NA | NA | NA | NA | NA | NA | NA | [168] |
MYH7 Het p.Glu848Gly | Patient |  − 75% |  − 30% |  − 10% | ± | Yes | NA | Impaired fractional shortening, maximal contraction velocity + 15% | [169] |
ACTC1 Het p.Glu99Lys | Patient |  + 300% (K1); − 50% (K2) | ±(K1); + 50% (K2) | NA | NA | NA | NA | Contraction velocity (K1 up, K2 down), TTP + 115% (K1), CTD90 + 31.4% (K1), increased arrhythmias (K2), increased DAD (K1) | [170] |
MYH7 Het p.Arg403Gln; MYBPC3 Het p.Trp792ValfsX41; MYBPC3 Het p.Arg502Trp | Patient |  + 50 − 100% | ± |  + 20 − 65% |  + 30% |  + 60% | NA | Maximal contraction velocity + 79%–121%, highly activated p53 and p21 pathways, elevated mitochondrial content, increased ROS, and elevated ratio of ADP/ATP | [171] |
MYBPC3 Het p.Arg943x; MYBPC3 Het p.Arg1073Pro | Patient and isogenic | ±(Het); − 60% (Hom) | NA | NA | ± | ± | NA | Increased diastolic [Ca2+]i, slower Ca2+ decay, decreased contraction and relaxation velocity (Hom), downregulated expression of ATP2A2 | [172] |
ACTN2 Het p.Thr247Met | Patient |  + 19% | ± |  + 17% |  + 80% |  + 38% | NA | Increased Ca2 + sensitivity, elevated action potential amplitude, APD prolongation + 50%, increased ICa, transcript levels of ACTN2 + 200% | [173] |
MYL2 Het p.Arg58Gln | Patient | NA | NA |  + 90% |  + 29% |  + 100% | NA | Diastolic [Ca2+]i − 23%, peak Ca2+ transients − 45%, Ca2+ decay tau + 38%, ICa − 45%, increased arrhythmias | [174] |
MYH7 Het p.Arg663His; MYBPC3 Het p.Val321Met; MYBPC3 Het p.Val219Leu; TNNT2 Het p.Arg92Trp | Patient and isogenic | NA | NA | NA | NA | NA | NA | Increased diastolic [Ca2+]i and Ca2 + sensitivity, slower Ca2+ decay, reduced NCX function, decreased sarcomere length, increased maximal contraction velocity, decreased maximal relaxation velocity | [88] |
MYH7 Het/Hom c. 9123C > T; ACTC1 Het/Hom c. 301 G > A | Patient and isogenic |  − 32 − 53% (M); + 41% (A) |  + 10% (M);  + 47% (A) |  + 20% (M); + 38% (A) | Increased | Yes | NA | Increased diastolic [Ca2+]i (M, not A), elevated systolic [Ca2+]i, increased spontaneous beat rate (M, not A), increased arrhythmias, basal and maximal respirations up | [175] |
MYH7 Het p.Arg403Gln | Patient |  + 100% | NA | NA |  + 33% | NA | NA | Increased maximal contraction and relaxation velocity | [176] |
MYBPC3 Het c.1377delC | Patient | NA | NA | NA | NA | NA | NA | NA | [177] |
MYBPC3 Het Δ25/ p.Asp389Val;  MYH7 Het p.Arg243Cys | Patient | NA | ± |  + 24% (MYBPC3); + 39% (MYH7) |  + 76% (MYBPC3); + 180% (MYH7) | NA | 23% vs. 6% (MYBPC3); 54% vs. 6% (MYH7) | Increased Ca2+ decay tau, increased arrhythmias, relaxation velocity down | [178] |