Clinical parameters and variants found in HCM patients
| Gender | Age at diagnosis (years) | MLVWT (mm) | SCD in family | Gene | Var g. | Reference sequence | Var c. | Var p. | PolyPhen2 HumVar | PolyPhen2 HumDiv | Grantham dist | SIFT | AGVGD | Freq in EVS (variant alles/wt alleles) | Classification* | Additional information | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Patient 20 | M | ? | ? | ? | TPM1 | 63356265 A>G | NM_001018020.1 | 775A>G | p.Lys259Glu | Not reliable | Not reliable | 56 | 0.00 | C55 | 4/10 754 | VUS2 | No (not present in transcript NM_000366.5) |
| Patient 21 | M | 65 | 17 | No | – | – | – | – | – | – | – | – | – | – | – | – | |
| Patient 22 | F | 58 | 16 | Yes | VCL | 75854219 G>A | NM_014000.2 | 1543G>A | p.Gly515Ser | Probably damaging | Probably damaging | 56 | 0.00 | C55 | Not found | VUS2 | No (splicing could be affected) |
| Patient 23 | M | 62 | 15 | No | – | – | – | – | – | – | – | – | – | – | – | – | |
| Patient 24 | M | 79 | 17 | No | – | – | – | – | – | – | – | – | – | – | – | – | |
| Patient 25 | M | 44 | 20 | ? | LDB3 | 88441437 C>T | NM_007078.2 | 566C>T | p.Ser189Leu | Benign | Benign | 145 | 0.1 | C0 | 2/10 806 | VUS3 | DCM/LVNC family (called S196L), co-segregation in 4 affected members.23 Functionally tested.24 25 |
| MYBPC3 | 47354463 T>C | NM_000256.3 | 3392T>C | p.Ile1131Thr | Benign | Possibly damaging | 89 | 0.03 | C55 | 7/12 331 | VUS1 | 3 other DCM/NCCM index patients† (one of them together with the pathogenic Dutch founder mutation c.2373dup in MYBPC322; in another family no co-segregation in an affected uncle) | |||||
| Patient 26 | M | 56 | 23 | No | – | – | – | – | – | – | – | – | – | – | – | – | |
| Patient 27 | M | 50 | 19 | No | – | – | – | – | – | – | – | – | – | – | – | – | |
| Patient 28 | M | 67 | 28 | ? | TNNT2 | 201328349 C>T | NM_000364.2 | 877C>T | p.Arg293Cys | Probably damaging | Probably damaging | 180 | 0.00 | C0 | Not found | VUS3 | 3 HCM index patients (called R286C).20 21 3 HCM index patients† |
Variants in the genes highlighted in bold are variants that were found on top of the variants that were already detected by Sanger sequencing. The variant present in VCL (patient 22) introduced a loss of a splice site on top of the amino acid change.
*For further details see Methods section.
†Identified in cardiomyopathy patients analysed during routine diagnostics in our laboratory.
DCM, dilated cardiomyopathy; HCM, hypertrophic cardiomyopathy; LVNC, left ventricular non-compaction; MLVWT, maximal left ventricular wall thickness; n.a., not available; NCCM, non-compaction cardiomyopathy; SCD, sudden cardiac death; ?, unknown or no exact measurement performed.