Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24068 | 72427;72428;72429 | chr2:178573930;178573929;178573928 | chr2:179438657;179438656;179438655 |
| N2AB | 22427 | 67504;67505;67506 | chr2:178573930;178573929;178573928 | chr2:179438657;179438656;179438655 |
| N2A | 21500 | 64723;64724;64725 | chr2:178573930;178573929;178573928 | chr2:179438657;179438656;179438655 |
| N2B | 15003 | 45232;45233;45234 | chr2:178573930;178573929;178573928 | chr2:179438657;179438656;179438655 |
| Novex-1 | 15128 | 45607;45608;45609 | chr2:178573930;178573929;178573928 | chr2:179438657;179438656;179438655 |
| Novex-2 | 15195 | 45808;45809;45810 | chr2:178573930;178573929;178573928 | chr2:179438657;179438656;179438655 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/E | rs766736138  |
0.488 | 0.999 | N | 0.678 | 0.285 | 0.478828542108 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| K/E | rs766736138 |
0.488 | 0.999 | N | 0.678 | 0.285 | 0.478828542108 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| K/E | rs766736138 |
0.488 | 0.999 | N | 0.678 | 0.285 | 0.478828542108 | gnomAD-4.0.0 | 3.09964E-06 | None | None | None | None | N | None | 0 | 3.33489E-05 | None | 0 | 0 | None | 0 | 0 | 2.54352E-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 | 0.2566 | likely_benign | 0.2865 | benign | 0.029 | Stabilizing | 0.999 | D | 0.68 | prob.neutral | None | None | None | None | N |
| K/C | 0.5062 | ambiguous | 0.5472 | ambiguous | -0.317 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | N |
| K/D | 0.4073 | ambiguous | 0.4644 | ambiguous | -0.037 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | N |
| K/E | 0.121 | likely_benign | 0.1427 | benign | -0.038 | Destabilizing | 0.999 | D | 0.678 | prob.neutral | N | 0.495674592 | None | None | N |
| K/F | 0.5612 | ambiguous | 0.5992 | pathogenic | -0.244 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | N |
| K/G | 0.359 | ambiguous | 0.4088 | ambiguous | -0.14 | Destabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | N |
| K/H | 0.2319 | likely_benign | 0.2478 | benign | -0.341 | Destabilizing | 1.0 | D | 0.672 | neutral | None | None | None | None | N |
| K/I | 0.1791 | likely_benign | 0.2008 | benign | 0.391 | Stabilizing | 1.0 | D | 0.721 | prob.delet. | D | 0.533926336 | None | None | N |
| K/L | 0.2334 | likely_benign | 0.2549 | benign | 0.391 | Stabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | N |
| K/M | 0.1503 | likely_benign | 0.1651 | benign | 0.1 | Stabilizing | 1.0 | D | 0.666 | neutral | None | None | None | None | N |
| K/N | 0.26 | likely_benign | 0.3014 | benign | 0.112 | Stabilizing | 1.0 | D | 0.705 | prob.neutral | N | 0.486670742 | None | None | N |
| K/P | 0.8454 | likely_pathogenic | 0.8747 | pathogenic | 0.297 | Stabilizing | 1.0 | D | 0.69 | prob.neutral | None | None | None | None | N |
| K/Q | 0.1029 | likely_benign | 0.1119 | benign | -0.034 | Destabilizing | 1.0 | D | 0.688 | prob.neutral | N | 0.495231875 | None | None | N |
| K/R | 0.0755 | likely_benign | 0.0778 | benign | -0.067 | Destabilizing | 0.999 | D | 0.611 | neutral | N | 0.482689439 | None | None | N |
| K/S | 0.2969 | likely_benign | 0.3385 | benign | -0.321 | Destabilizing | 0.999 | D | 0.655 | neutral | None | None | None | None | N |
| K/T | 0.1408 | likely_benign | 0.1632 | benign | -0.183 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | N | 0.485758916 | None | None | N |
| K/V | 0.1739 | likely_benign | 0.1977 | benign | 0.297 | Stabilizing | 1.0 | D | 0.708 | prob.delet. | None | None | None | None | N |
| K/W | 0.6156 | likely_pathogenic | 0.6561 | pathogenic | -0.307 | Destabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | N |
| K/Y | 0.4625 | ambiguous | 0.5018 | ambiguous | 0.054 | Stabilizing | 1.0 | D | 0.677 | 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.