Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1140 | 3643;3644;3645 | chr2:178781226;178781225;178781224 | chr2:179645953;179645952;179645951 |
| N2AB | 1140 | 3643;3644;3645 | chr2:178781226;178781225;178781224 | chr2:179645953;179645952;179645951 |
| N2A | 1140 | 3643;3644;3645 | chr2:178781226;178781225;178781224 | chr2:179645953;179645952;179645951 |
| N2B | 1094 | 3505;3506;3507 | chr2:178781226;178781225;178781224 | chr2:179645953;179645952;179645951 |
| Novex-1 | 1094 | 3505;3506;3507 | chr2:178781226;178781225;178781224 | chr2:179645953;179645952;179645951 |
| Novex-2 | 1094 | 3505;3506;3507 | chr2:178781226;178781225;178781224 | chr2:179645953;179645952;179645951 |
| Novex-3 | 1140 | 3643;3644;3645 | chr2:178781226;178781225;178781224 | chr2:179645953;179645952;179645951 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/M | rs769789570  |
-0.17 | 0.915 | N | 0.561 | 0.235 | None | gnomAD-2.1.1 | 1.99E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.45E-05 | None | 0 | None | 0 | 3.52E-05 | 0 |
| K/M | rs769789570 |
-0.17 | 0.915 | N | 0.561 | 0.235 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| K/M | rs769789570 |
-0.17 | 0.915 | N | 0.561 | 0.235 | None | gnomAD-4.0.0 | 9.91349E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.27121E-05 | 0 | 1.60056E-05 |
| K/N | None | None | 0.117 | N | 0.495 | 0.105 | 0.0884992946249 | gnomAD-4.0.0 | 1.5908E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85687E-06 | 0 | 0 |
| K/Q | rs1561345560 |
None | 0.062 | N | 0.533 | 0.177 | 0.183819452728 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.81E-06 | 0 |
| K/Q | rs1561345560 |
None | 0.062 | N | 0.533 | 0.177 | 0.183819452728 | gnomAD-4.0.0 | 1.5908E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85687E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.4808 | ambiguous | 0.4414 | ambiguous | -0.546 | Destabilizing | 0.035 | N | 0.478 | neutral | None | None | None | None | N |
| K/C | 0.6729 | likely_pathogenic | 0.6344 | pathogenic | -0.568 | Destabilizing | 0.935 | D | 0.7 | prob.neutral | None | None | None | None | N |
| K/D | 0.7748 | likely_pathogenic | 0.7412 | pathogenic | -0.548 | Destabilizing | 0.149 | N | 0.488 | neutral | None | None | None | None | N |
| K/E | 0.2508 | likely_benign | 0.2354 | benign | -0.435 | Destabilizing | 0.062 | N | 0.575 | neutral | N | 0.44653799 | None | None | N |
| K/F | 0.8253 | likely_pathogenic | 0.7975 | pathogenic | -0.235 | Destabilizing | 0.555 | D | 0.667 | neutral | None | None | None | None | N |
| K/G | 0.6551 | likely_pathogenic | 0.6161 | pathogenic | -0.933 | Destabilizing | 0.149 | N | 0.547 | neutral | None | None | None | None | N |
| K/H | 0.2749 | likely_benign | 0.2651 | benign | -1.393 | Destabilizing | 0.555 | D | 0.558 | neutral | None | None | None | None | N |
| K/I | 0.3537 | ambiguous | 0.3174 | benign | 0.463 | Stabilizing | 0.555 | D | 0.641 | neutral | None | None | None | None | N |
| K/L | 0.3982 | ambiguous | 0.3659 | ambiguous | 0.463 | Stabilizing | 0.149 | N | 0.523 | neutral | None | None | None | None | N |
| K/M | 0.2487 | likely_benign | 0.2296 | benign | 0.454 | Stabilizing | 0.915 | D | 0.561 | neutral | N | 0.491753705 | None | None | N |
| K/N | 0.483 | ambiguous | 0.447 | ambiguous | -0.638 | Destabilizing | 0.117 | N | 0.495 | neutral | N | 0.461923719 | None | None | N |
| K/P | 0.9896 | likely_pathogenic | 0.9869 | pathogenic | 0.157 | Stabilizing | 0.555 | D | 0.535 | neutral | None | None | None | None | N |
| K/Q | 0.1155 | likely_benign | 0.1117 | benign | -0.715 | Destabilizing | 0.062 | N | 0.533 | neutral | N | 0.458469849 | None | None | N |
| K/R | 0.0797 | likely_benign | 0.0795 | benign | -0.785 | Destabilizing | None | N | 0.264 | neutral | N | 0.451410805 | None | None | N |
| K/S | 0.4309 | ambiguous | 0.4033 | ambiguous | -1.213 | Destabilizing | 0.007 | N | 0.475 | neutral | None | None | None | None | N |
| K/T | 0.1726 | likely_benign | 0.1581 | benign | -0.893 | Destabilizing | 0.062 | N | 0.471 | neutral | N | 0.396016323 | None | None | N |
| K/V | 0.3482 | ambiguous | 0.3164 | benign | 0.157 | Stabilizing | 0.38 | N | 0.593 | neutral | None | None | None | None | N |
| K/W | 0.7804 | likely_pathogenic | 0.7577 | pathogenic | -0.156 | Destabilizing | 0.935 | D | 0.72 | prob.delet. | None | None | None | None | N |
| K/Y | 0.6693 | likely_pathogenic | 0.6376 | pathogenic | 0.159 | Stabilizing | 0.555 | D | 0.617 | 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.