Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17989 | 54190;54191;54192 | chr2:178605212;178605211;178605210 | chr2:179469939;179469938;179469937 |
| N2AB | 16348 | 49267;49268;49269 | chr2:178605212;178605211;178605210 | chr2:179469939;179469938;179469937 |
| N2A | 15421 | 46486;46487;46488 | chr2:178605212;178605211;178605210 | chr2:179469939;179469938;179469937 |
| N2B | 8924 | 26995;26996;26997 | chr2:178605212;178605211;178605210 | chr2:179469939;179469938;179469937 |
| Novex-1 | 9049 | 27370;27371;27372 | chr2:178605212;178605211;178605210 | chr2:179469939;179469938;179469937 |
| Novex-2 | 9116 | 27571;27572;27573 | chr2:178605212;178605211;178605210 | chr2:179469939;179469938;179469937 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/N | rs1060500481  |
None | 0.322 | N | 0.393 | 0.171 | 0.223847106136 | gnomAD-4.0.0 | 1.59521E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.03361E-05 |
| D/Y | None | None | 0.999 | N | 0.736 | 0.485 | 0.68628391497 | gnomAD-4.0.0 | 1.59521E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86398E-06 | 0 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2833 | likely_benign | 0.2382 | benign | -0.207 | Destabilizing | 0.939 | D | 0.673 | neutral | N | 0.456540201 | None | None | I |
| D/C | 0.8236 | likely_pathogenic | 0.7667 | pathogenic | 0.025 | Stabilizing | 0.999 | D | 0.701 | prob.neutral | None | None | None | None | I |
| D/E | 0.2229 | likely_benign | 0.1734 | benign | -0.47 | Destabilizing | 0.046 | N | 0.255 | neutral | N | 0.40853561 | None | None | I |
| D/F | 0.6503 | likely_pathogenic | 0.5677 | pathogenic | -0.193 | Destabilizing | 0.999 | D | 0.734 | prob.delet. | None | None | None | None | I |
| D/G | 0.4873 | ambiguous | 0.429 | ambiguous | -0.445 | Destabilizing | 0.939 | D | 0.607 | neutral | N | 0.503814073 | None | None | I |
| D/H | 0.4421 | ambiguous | 0.3611 | ambiguous | -0.314 | Destabilizing | 0.998 | D | 0.725 | prob.delet. | N | 0.480033136 | None | None | I |
| D/I | 0.3777 | ambiguous | 0.2868 | benign | 0.377 | Stabilizing | 0.993 | D | 0.755 | deleterious | None | None | None | None | I |
| D/K | 0.6447 | likely_pathogenic | 0.539 | ambiguous | -0.001 | Destabilizing | 0.91 | D | 0.649 | neutral | None | None | None | None | I |
| D/L | 0.466 | ambiguous | 0.3984 | ambiguous | 0.377 | Stabilizing | 0.986 | D | 0.748 | deleterious | None | None | None | None | I |
| D/M | 0.6498 | likely_pathogenic | 0.5559 | ambiguous | 0.563 | Stabilizing | 0.999 | D | 0.723 | prob.delet. | None | None | None | None | I |
| D/N | 0.1648 | likely_benign | 0.126 | benign | -0.168 | Destabilizing | 0.322 | N | 0.393 | neutral | N | 0.472067013 | None | None | I |
| D/P | 0.9757 | likely_pathogenic | 0.9678 | pathogenic | 0.206 | Stabilizing | 0.993 | D | 0.737 | prob.delet. | None | None | None | None | I |
| D/Q | 0.5349 | ambiguous | 0.4467 | ambiguous | -0.124 | Destabilizing | 0.973 | D | 0.635 | neutral | None | None | None | None | I |
| D/R | 0.6918 | likely_pathogenic | 0.6053 | pathogenic | 0.128 | Stabilizing | 0.986 | D | 0.751 | deleterious | None | None | None | None | I |
| D/S | 0.2336 | likely_benign | 0.187 | benign | -0.32 | Destabilizing | 0.953 | D | 0.503 | neutral | None | None | None | None | I |
| D/T | 0.3168 | likely_benign | 0.2563 | benign | -0.148 | Destabilizing | 0.986 | D | 0.705 | prob.neutral | None | None | None | None | I |
| D/V | 0.2343 | likely_benign | 0.1858 | benign | 0.206 | Stabilizing | 0.991 | D | 0.747 | deleterious | N | 0.466373192 | None | None | I |
| D/W | 0.9299 | likely_pathogenic | 0.9122 | pathogenic | -0.128 | Destabilizing | 0.999 | D | 0.674 | neutral | None | None | None | None | I |
| D/Y | 0.3488 | ambiguous | 0.2964 | benign | 0.014 | Stabilizing | 0.999 | D | 0.736 | prob.delet. | N | 0.495367948 | None | None | I |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.