Table 2.
Nonsynonymous nucleotide alterations in six FDC/IDC genes.
| Gene/Proband | Exon | Nucleotide change* | Amino acid change | Conservation† | Segregation| | Disease‐associated? | Diagnosis, FDC¶ or IDC∥ | Previously reported cardiovascular disease | Reference |
|---|---|---|---|---|---|---|---|---|---|
| A. MYH7, β‐myosin heavy chain | |||||||||
| A.1# | 8 | 4231C>T | Arg237Trp | Yes | Possibly | FDC | |||
| A.2 | 23 | 11900G>C | Val964Leu | Yes | Possibly | FDC | |||
| A.3 | 23 | 11919C>T | Ala970Val | Yes | Possibly | FDC | |||
| A.4 | 25 | 13547C>T | Arg1045Cys | Yes | Possibly | IDC | |||
| A.5 | 26 | 14831G>T | Asp1096Tyr | Yes | Possibly | FDC | |||
| A.6 | 26 | 14831G>T | Asp1096Tyr | Yes | Possibly | IDC | |||
| A.7 | 30 | 17536C>T | Arg1359Cys | Yes | Possibly | IDC | |||
| A.8 | 32 | 18666C>T | Arg1500Trp | Yes | Yes | Likely | FDC | DCM | 34 |
| A.9 | 34 | 19738G>A | Glu1619Lys | Yes | Possibly | FDC | |||
| A.10 | 35 | 20125G>A | Val1691Met | Yes | Possibly | FDC | HCM | 35 | |
| A.11‡ | 37 | 20709G>C** | Gly1808Ala | Yes | Likely | FDC | |||
| A.12 | 39 | 21994C>G | His1901Gln | Yes | Possibly | FDC | Skeletal myopathy | 36 | |
| A.13 | 38 | 21766G>A | Arg1863Gln | Yes | Possibly | FDC | |||
| B. TNNT2, cardiac troponin T | |||||||||
| B.1 | 11/10 | 13712C>G | Arg134Gly | Yes | Yes | Likely | FDC | ||
| B.2 | 11/10 | 13763C>T** | Arg151Cys | Yes | Likely | IDC | |||
| B.3 | 12/11 | 14679G>A | Arg159Gln | Yes | Possibly | IDC | |||
| B.4 | 13 | 16080C>T | Arg205Trp | Yes | Likely | IDC | DCM | 18 | |
| B.5 | 13 | 16096_16098delAGA | Lys210del | N/A | Likely | FDC | DCM | 10, 11, 18, 37 | |
| B.6 | 13 | 16096_16098delAGA | Lys210del | N/A | Yes | Likely | FDC | DCM | 10, 11, 18, 37 |
| B.7 | 13 | 16096_16098delAGA | Lys210del | N/A | Yes | Likely | FDC | DCM | 10, 11, 18, 37 |
| B.8 | 13 | 16096_16098delAGA | Lys210del | N/A | Yes | Likely | FDC | DCM | 10, 11, 18, 37 |
| B.9‡ | 14 | 16742G>T | Glu244Asp | Yes | Possibly | IDC | HCM | 38 | |
| C. SCN5A, cardiac sodium channel | |||||||||
| C.1 | 6 | 36665C>T | Ser216Leu | Yes | Possibly | IDC | Long QT | 39 | |
| C.2 | 6 | 36665C>T | Ser216Leu | Yes | Possibly | IDC | Long QT | ||
| C.3 | 6 | 36683G>A | Arg222GLN | Yes | Yes | Likely | FDC | ||
| C.4 | 12 | 46439G>A | Arg526His | Yes | No | Unlikely | IDC | Brugada Syndrome | 40 |
| C.5§ | 12 | 46577C>A | Ala572Asp | No | No | Unlikely | FDC | Long QT | 41 |
| C.6 | 13 | 51466C>T | Pro648Leu | Yes | Possibly | FDC | Long QT | 42 | |
| C.7† | 28 | 99599T>C | Ile1835Thr | Yes | Yes | Likely | FDC | ||
| C.8 | 28 | 100108C>G | Pro2005Ala | Yes | Possibly | IDC | Long QT | 43 | |
| D. TCAP, titin‐cap or telethonin | |||||||||
| D.1 | 1 | 1630G>A | Arg18Gln | Yes | Possibly | IDC | |||
| D.2 | 2 | 1968G>A | Glu49Lys | Yes | Possibly | IDC | |||
| D.3∥∥ | 2 | 2244C>G | Pro141Ala | Yes | No | Unlikely | IDC | ||
| E. LDB3, limb domain‐binding 3 | |||||||||
| E.1 | 8 | 41461G>A | Ala371Thr | No | Unlikely | FDC | |||
| E.2 | 12 | 57781G>A | Ala698Thr | Yes | Possibly | IDC | |||
| E.3# | 12 | 57781G>A | Ala698Thr | Yes | Possibly | FDC | |||
| F. CSRP3, cysteine‐ and glycine‐rich protein 3 | |||||||||
| F.1 | 3 | 14108G>A | Gly72Arg | Yes | Possibly | IDC | |||
*Nucleotide numbering is per the SeattleSNPs resequencing service. Amino acid numbering is per previous publications. † Human sequence was compared to rat (r) and mouse (m); N/A, not applicable. ¶Probable FDC was considered FDC, and ∥possible FDC was considered IDC (see Methods). |Segregation means multiple affected carrying mutation and/or multiple nonaffected not carrying mutation; entry left blank because of insufficient clinical data and/or DNA specimens to assess segregation. #A.1 and E.3 is same proband with compound heterozygosity. **Homozygous mutation; Caucasian of Hispanic descent. ‡African‐American. §Proband carries likely disease ‐causing presenilin 2 mutation. ∥∥Proband carries likely disease‐causing lamin A/C mutation.