Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15634 | 47125;47126;47127 | chr2:178618650;178618649;178618648 | chr2:179483377;179483376;179483375 |
| N2AB | 13993 | 42202;42203;42204 | chr2:178618650;178618649;178618648 | chr2:179483377;179483376;179483375 |
| N2A | 13066 | 39421;39422;39423 | chr2:178618650;178618649;178618648 | chr2:179483377;179483376;179483375 |
| N2B | 6569 | 19930;19931;19932 | chr2:178618650;178618649;178618648 | chr2:179483377;179483376;179483375 |
| Novex-1 | 6694 | 20305;20306;20307 | chr2:178618650;178618649;178618648 | chr2:179483377;179483376;179483375 |
| Novex-2 | 6761 | 20506;20507;20508 | chr2:178618650;178618649;178618648 | chr2:179483377;179483376;179483375 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/K | None | None | 0.78 | N | 0.606 | 0.107 | 0.329540904979 | gnomAD-4.0.0 | 1.5944E-06 | None | None | None | None | N | None | 0 | 0 | None | 4.77692E-05 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/S | None | None | 0.103 | N | 0.343 | 0.145 | 0.0611884634855 | gnomAD-4.0.0 | 6.84754E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99986E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.4711 | ambiguous | 0.5295 | ambiguous | -0.861 | Destabilizing | 0.702 | D | 0.621 | neutral | None | None | None | None | N |
| R/C | 0.2022 | likely_benign | 0.2573 | benign | -0.848 | Destabilizing | 0.999 | D | 0.683 | prob.neutral | None | None | None | None | N |
| R/D | 0.681 | likely_pathogenic | 0.7292 | pathogenic | -0.01 | Destabilizing | 0.976 | D | 0.641 | neutral | None | None | None | None | N |
| R/E | 0.413 | ambiguous | 0.4652 | ambiguous | 0.128 | Stabilizing | 0.919 | D | 0.617 | neutral | None | None | None | None | N |
| R/F | 0.599 | likely_pathogenic | 0.6536 | pathogenic | -0.679 | Destabilizing | 0.988 | D | 0.691 | prob.neutral | None | None | None | None | N |
| R/G | 0.4066 | ambiguous | 0.4693 | ambiguous | -1.17 | Destabilizing | 0.811 | D | 0.627 | neutral | N | 0.512227325 | None | None | N |
| R/H | 0.1199 | likely_benign | 0.1433 | benign | -1.505 | Destabilizing | 0.076 | N | 0.283 | neutral | None | None | None | None | N |
| R/I | 0.2528 | likely_benign | 0.279 | benign | -0.029 | Destabilizing | 0.988 | D | 0.692 | prob.neutral | None | None | None | None | N |
| R/K | 0.1209 | likely_benign | 0.1356 | benign | -0.754 | Destabilizing | 0.78 | D | 0.606 | neutral | N | 0.502407712 | None | None | N |
| R/L | 0.2767 | likely_benign | 0.3228 | benign | -0.029 | Destabilizing | 0.919 | D | 0.635 | neutral | None | None | None | None | N |
| R/M | 0.3168 | likely_benign | 0.3604 | ambiguous | -0.443 | Destabilizing | 0.999 | D | 0.673 | neutral | N | 0.51283326 | None | None | N |
| R/N | 0.5065 | ambiguous | 0.5548 | ambiguous | -0.35 | Destabilizing | 0.919 | D | 0.625 | neutral | None | None | None | None | N |
| R/P | 0.6624 | likely_pathogenic | 0.707 | pathogenic | -0.286 | Destabilizing | 0.988 | D | 0.702 | prob.neutral | None | None | None | None | N |
| R/Q | 0.1165 | likely_benign | 0.1334 | benign | -0.46 | Destabilizing | 0.988 | D | 0.649 | neutral | None | None | None | None | N |
| R/S | 0.5306 | ambiguous | 0.587 | pathogenic | -1.123 | Destabilizing | 0.103 | N | 0.343 | neutral | N | 0.507081171 | None | None | N |
| R/T | 0.2501 | likely_benign | 0.2696 | benign | -0.793 | Destabilizing | 0.811 | D | 0.653 | neutral | N | 0.508140706 | None | None | N |
| R/V | 0.3538 | ambiguous | 0.4024 | ambiguous | -0.286 | Destabilizing | 0.976 | D | 0.666 | neutral | None | None | None | None | N |
| R/W | 0.2373 | likely_benign | 0.2784 | benign | -0.352 | Destabilizing | 0.999 | D | 0.687 | prob.neutral | N | 0.513657448 | None | None | N |
| R/Y | 0.4069 | ambiguous | 0.4883 | ambiguous | -0.071 | Destabilizing | 0.976 | D | 0.705 | prob.neutral | None | None | None | None | N |
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.