Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29326 | 88201;88202;88203 | chr2:178557286;178557285;178557284 | chr2:179422013;179422012;179422011 |
| N2AB | 27685 | 83278;83279;83280 | chr2:178557286;178557285;178557284 | chr2:179422013;179422012;179422011 |
| N2A | 26758 | 80497;80498;80499 | chr2:178557286;178557285;178557284 | chr2:179422013;179422012;179422011 |
| N2B | 20261 | 61006;61007;61008 | chr2:178557286;178557285;178557284 | chr2:179422013;179422012;179422011 |
| Novex-1 | 20386 | 61381;61382;61383 | chr2:178557286;178557285;178557284 | chr2:179422013;179422012;179422011 |
| Novex-2 | 20453 | 61582;61583;61584 | chr2:178557286;178557285;178557284 | chr2:179422013;179422012;179422011 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/R | rs1450387071  |
-0.584 | 0.087 | N | 0.67 | 0.307 | 0.336647302497 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| P/R | rs1450387071 |
-0.584 | 0.087 | N | 0.67 | 0.307 | 0.336647302497 | gnomAD-4.0.0 | 3.18235E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.71549E-06 | 0 | 0 |
| P/S | rs1190882464 |
-1.349 | None | N | 0.419 | 0.105 | 0.0884992946249 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| P/S | rs1190882464 |
-1.349 | None | N | 0.419 | 0.105 | 0.0884992946249 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0702 | likely_benign | 0.0707 | benign | -1.663 | Destabilizing | None | N | 0.424 | neutral | N | 0.46337488 | None | None | I |
| P/C | 0.3773 | ambiguous | 0.4403 | ambiguous | -0.933 | Destabilizing | 0.492 | N | 0.735 | deleterious | None | None | None | None | I |
| P/D | 0.7511 | likely_pathogenic | 0.8048 | pathogenic | -1.454 | Destabilizing | 0.035 | N | 0.633 | neutral | None | None | None | None | I |
| P/E | 0.5119 | ambiguous | 0.5731 | pathogenic | -1.462 | Destabilizing | 0.035 | N | 0.638 | neutral | None | None | None | None | I |
| P/F | 0.5645 | likely_pathogenic | 0.6359 | pathogenic | -1.379 | Destabilizing | 0.112 | N | 0.709 | prob.delet. | None | None | None | None | I |
| P/G | 0.3753 | ambiguous | 0.3918 | ambiguous | -1.98 | Destabilizing | 0.007 | N | 0.555 | neutral | None | None | None | None | I |
| P/H | 0.3329 | likely_benign | 0.4019 | ambiguous | -1.476 | Destabilizing | 0.69 | D | 0.67 | prob.neutral | N | 0.505411248 | None | None | I |
| P/I | 0.2301 | likely_benign | 0.2771 | benign | -0.886 | Destabilizing | 0.018 | N | 0.609 | neutral | None | None | None | None | I |
| P/K | 0.5142 | ambiguous | 0.5893 | pathogenic | -1.207 | Destabilizing | 0.035 | N | 0.644 | neutral | None | None | None | None | I |
| P/L | 0.1562 | likely_benign | 0.1877 | benign | -0.886 | Destabilizing | None | N | 0.539 | neutral | N | 0.512590192 | None | None | I |
| P/M | 0.3239 | likely_benign | 0.3842 | ambiguous | -0.561 | Destabilizing | 0.112 | N | 0.642 | neutral | None | None | None | None | I |
| P/N | 0.4591 | ambiguous | 0.516 | ambiguous | -0.936 | Destabilizing | 0.112 | N | 0.669 | prob.neutral | None | None | None | None | I |
| P/Q | 0.2684 | likely_benign | 0.3141 | benign | -1.147 | Destabilizing | 0.112 | N | 0.655 | prob.neutral | None | None | None | None | I |
| P/R | 0.3873 | ambiguous | 0.4529 | ambiguous | -0.643 | Destabilizing | 0.087 | N | 0.67 | prob.neutral | N | 0.498067414 | None | None | I |
| P/S | 0.1411 | likely_benign | 0.148 | benign | -1.466 | Destabilizing | None | N | 0.419 | neutral | N | 0.489849406 | None | None | I |
| P/T | 0.1089 | likely_benign | 0.122 | benign | -1.367 | Destabilizing | 0.006 | N | 0.545 | neutral | N | 0.482768718 | None | None | I |
| P/V | 0.153 | likely_benign | 0.1814 | benign | -1.112 | Destabilizing | None | N | 0.519 | neutral | None | None | None | None | I |
| P/W | 0.7994 | likely_pathogenic | 0.8441 | pathogenic | -1.538 | Destabilizing | 0.747 | D | 0.775 | deleterious | None | None | None | None | I |
| P/Y | 0.5974 | likely_pathogenic | 0.6706 | pathogenic | -1.272 | Destabilizing | 0.204 | N | 0.711 | prob.delet. | None | None | 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.