Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19546 | 58861;58862;58863 | chr2:178593664;178593663;178593662 | chr2:179458391;179458390;179458389 |
| N2AB | 17905 | 53938;53939;53940 | chr2:178593664;178593663;178593662 | chr2:179458391;179458390;179458389 |
| N2A | 16978 | 51157;51158;51159 | chr2:178593664;178593663;178593662 | chr2:179458391;179458390;179458389 |
| N2B | 10481 | 31666;31667;31668 | chr2:178593664;178593663;178593662 | chr2:179458391;179458390;179458389 |
| Novex-1 | 10606 | 32041;32042;32043 | chr2:178593664;178593663;178593662 | chr2:179458391;179458390;179458389 |
| Novex-2 | 10673 | 32242;32243;32244 | chr2:178593664;178593663;178593662 | chr2:179458391;179458390;179458389 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/Q | rs201840554  |
-0.224 | 1.0 | N | 0.673 | 0.354 | None | gnomAD-2.1.1 | 9.91836E-04 | None | None | None | None | N | None | 1.0508E-02 | 3.12181E-04 | None | 0 | 0 | None | 0 | None | 0 | 4.7E-05 | 8.44832E-04 |
| E/Q | rs201840554 |
-0.224 | 1.0 | N | 0.673 | 0.354 | None | gnomAD-3.1.2 | 2.93355E-03 | None | None | None | None | N | None | 1.04313E-02 | 3.93494E-04 | 0 | 0 | 0 | None | 0 | 0 | 8.83E-05 | 0 | 9.5511E-04 |
| E/Q | rs201840554 |
-0.224 | 1.0 | N | 0.673 | 0.354 | None | 1000 genomes | 2.19649E-03 | None | None | None | None | N | None | 8.3E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| E/Q | rs201840554 |
-0.224 | 1.0 | N | 0.673 | 0.354 | None | gnomAD-4.0.0 | 5.47979E-04 | None | None | None | None | N | None | 1.08272E-02 | 3.83794E-04 | None | 0 | 0 | None | 0 | 3.30469E-04 | 9.32537E-06 | 3.29468E-05 | 5.28372E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.2224 | likely_benign | 0.2257 | benign | -0.656 | Destabilizing | 0.999 | D | 0.653 | neutral | N | 0.470252694 | None | None | N |
| E/C | 0.929 | likely_pathogenic | 0.9318 | pathogenic | -0.2 | Destabilizing | 1.0 | D | 0.649 | neutral | None | None | None | None | N |
| E/D | 0.3426 | ambiguous | 0.3297 | benign | -0.684 | Destabilizing | 0.999 | D | 0.553 | neutral | N | 0.481207834 | None | None | N |
| E/F | 0.9259 | likely_pathogenic | 0.93 | pathogenic | -0.43 | Destabilizing | 1.0 | D | 0.616 | neutral | None | None | None | None | N |
| E/G | 0.3973 | ambiguous | 0.4135 | ambiguous | -0.918 | Destabilizing | 1.0 | D | 0.618 | neutral | N | 0.504338518 | None | None | N |
| E/H | 0.74 | likely_pathogenic | 0.7521 | pathogenic | -0.495 | Destabilizing | 1.0 | D | 0.623 | neutral | None | None | None | None | N |
| E/I | 0.5883 | likely_pathogenic | 0.5874 | pathogenic | 0.024 | Stabilizing | 1.0 | D | 0.629 | neutral | None | None | None | None | N |
| E/K | 0.3286 | likely_benign | 0.3541 | ambiguous | -0.063 | Destabilizing | 0.999 | D | 0.677 | prob.neutral | N | 0.47278759 | None | None | N |
| E/L | 0.6947 | likely_pathogenic | 0.6982 | pathogenic | 0.024 | Stabilizing | 1.0 | D | 0.633 | neutral | None | None | None | None | N |
| E/M | 0.7257 | likely_pathogenic | 0.7372 | pathogenic | 0.3 | Stabilizing | 1.0 | D | 0.591 | neutral | None | None | None | None | N |
| E/N | 0.6074 | likely_pathogenic | 0.5997 | pathogenic | -0.414 | Destabilizing | 1.0 | D | 0.684 | prob.neutral | None | None | None | None | N |
| E/P | 0.4619 | ambiguous | 0.4696 | ambiguous | -0.182 | Destabilizing | 1.0 | D | 0.635 | neutral | None | None | None | None | N |
| E/Q | 0.2461 | likely_benign | 0.2577 | benign | -0.366 | Destabilizing | 1.0 | D | 0.673 | neutral | N | 0.468432723 | None | None | N |
| E/R | 0.487 | ambiguous | 0.5207 | ambiguous | 0.137 | Stabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | N |
| E/S | 0.4073 | ambiguous | 0.4151 | ambiguous | -0.623 | Destabilizing | 0.999 | D | 0.69 | prob.neutral | None | None | None | None | N |
| E/T | 0.4498 | ambiguous | 0.4555 | ambiguous | -0.412 | Destabilizing | 1.0 | D | 0.656 | neutral | None | None | None | None | N |
| E/V | 0.3697 | ambiguous | 0.3754 | ambiguous | -0.182 | Destabilizing | 1.0 | D | 0.622 | neutral | N | 0.485980774 | None | None | N |
| E/W | 0.9706 | likely_pathogenic | 0.9731 | pathogenic | -0.229 | Destabilizing | 1.0 | D | 0.651 | neutral | None | None | None | None | N |
| E/Y | 0.8548 | likely_pathogenic | 0.8659 | pathogenic | -0.182 | Destabilizing | 1.0 | D | 0.603 | 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.