Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29585 | 88978;88979;88980 | chr2:178554594;178554593;178554592 | chr2:179419321;179419320;179419319 |
| N2AB | 27944 | 84055;84056;84057 | chr2:178554594;178554593;178554592 | chr2:179419321;179419320;179419319 |
| N2A | 27017 | 81274;81275;81276 | chr2:178554594;178554593;178554592 | chr2:179419321;179419320;179419319 |
| N2B | 20520 | 61783;61784;61785 | chr2:178554594;178554593;178554592 | chr2:179419321;179419320;179419319 |
| Novex-1 | 20645 | 62158;62159;62160 | chr2:178554594;178554593;178554592 | chr2:179419321;179419320;179419319 |
| Novex-2 | 20712 | 62359;62360;62361 | chr2:178554594;178554593;178554592 | chr2:179419321;179419320;179419319 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/F | rs752117968  |
-0.526 | 0.667 | N | 0.697 | 0.328 | 0.587207757887 | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.11445E-04 | None | 0 | None | 0 | 0 | 0 |
| S/F | rs752117968 |
-0.526 | 0.667 | N | 0.697 | 0.328 | 0.587207757887 | gnomAD-4.0.0 | 1.59105E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77408E-05 | None | 0 | 0 | 0 | 0 | 0 |
| S/P | None | None | 0.497 | N | 0.623 | 0.229 | 0.292423486923 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| S/T | None | None | 0.124 | N | 0.465 | 0.089 | 0.17258766438 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-06 | 0 | 0 |
| S/Y | None | None | 0.667 | N | 0.696 | 0.317 | 0.573614764001 | gnomAD-4.0.0 | 1.59105E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85778E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0891 | likely_benign | 0.0858 | benign | -0.448 | Destabilizing | 0.001 | N | 0.237 | neutral | N | 0.410527404 | None | None | N |
| S/C | 0.1309 | likely_benign | 0.1289 | benign | -0.385 | Destabilizing | 0.883 | D | 0.623 | neutral | D | 0.524524914 | None | None | N |
| S/D | 0.6144 | likely_pathogenic | 0.5483 | ambiguous | -0.119 | Destabilizing | 0.157 | N | 0.483 | neutral | None | None | None | None | N |
| S/E | 0.7244 | likely_pathogenic | 0.6721 | pathogenic | -0.074 | Destabilizing | 0.272 | N | 0.485 | neutral | None | None | None | None | N |
| S/F | 0.4903 | ambiguous | 0.4537 | ambiguous | -0.532 | Destabilizing | 0.667 | D | 0.697 | prob.neutral | N | 0.469624492 | None | None | N |
| S/G | 0.1751 | likely_benign | 0.1525 | benign | -0.742 | Destabilizing | 0.072 | N | 0.499 | neutral | None | None | None | None | N |
| S/H | 0.5569 | ambiguous | 0.5224 | ambiguous | -1.21 | Destabilizing | 0.909 | D | 0.622 | neutral | None | None | None | None | N |
| S/I | 0.5117 | ambiguous | 0.4564 | ambiguous | 0.232 | Stabilizing | 0.567 | D | 0.687 | prob.neutral | None | None | None | None | N |
| S/K | 0.8735 | likely_pathogenic | 0.8417 | pathogenic | -0.532 | Destabilizing | 0.272 | N | 0.487 | neutral | None | None | None | None | N |
| S/L | 0.2014 | likely_benign | 0.1845 | benign | 0.232 | Stabilizing | 0.157 | N | 0.595 | neutral | None | None | None | None | N |
| S/M | 0.3316 | likely_benign | 0.3069 | benign | 0.216 | Stabilizing | 0.909 | D | 0.615 | neutral | None | None | None | None | N |
| S/N | 0.326 | likely_benign | 0.2858 | benign | -0.66 | Destabilizing | 0.005 | N | 0.304 | neutral | None | None | None | None | N |
| S/P | 0.9573 | likely_pathogenic | 0.9438 | pathogenic | 0.042 | Stabilizing | 0.497 | N | 0.623 | neutral | N | 0.501205337 | None | None | N |
| S/Q | 0.6893 | likely_pathogenic | 0.6565 | pathogenic | -0.64 | Destabilizing | 0.726 | D | 0.557 | neutral | None | None | None | None | N |
| S/R | 0.8428 | likely_pathogenic | 0.8099 | pathogenic | -0.589 | Destabilizing | 0.567 | D | 0.616 | neutral | None | None | None | None | N |
| S/T | 0.1199 | likely_benign | 0.113 | benign | -0.568 | Destabilizing | 0.124 | N | 0.465 | neutral | N | 0.453640676 | None | None | N |
| S/V | 0.3667 | ambiguous | 0.3293 | benign | 0.042 | Stabilizing | 0.396 | N | 0.615 | neutral | None | None | None | None | N |
| S/W | 0.6013 | likely_pathogenic | 0.5757 | pathogenic | -0.634 | Destabilizing | 0.968 | D | 0.705 | prob.neutral | None | None | None | None | N |
| S/Y | 0.3934 | ambiguous | 0.3655 | ambiguous | -0.292 | Destabilizing | 0.667 | D | 0.696 | prob.neutral | N | 0.486102598 | 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.