Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23954 | 72085;72086;72087 | chr2:178574272;178574271;178574270 | chr2:179438999;179438998;179438997 |
| N2AB | 22313 | 67162;67163;67164 | chr2:178574272;178574271;178574270 | chr2:179438999;179438998;179438997 |
| N2A | 21386 | 64381;64382;64383 | chr2:178574272;178574271;178574270 | chr2:179438999;179438998;179438997 |
| N2B | 14889 | 44890;44891;44892 | chr2:178574272;178574271;178574270 | chr2:179438999;179438998;179438997 |
| Novex-1 | 15014 | 45265;45266;45267 | chr2:178574272;178574271;178574270 | chr2:179438999;179438998;179438997 |
| Novex-2 | 15081 | 45466;45467;45468 | chr2:178574272;178574271;178574270 | chr2:179438999;179438998;179438997 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/L | rs1415995155  |
-1.348 | 0.822 | N | 0.601 | 0.249 | 0.355450299083 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | I | None | 1.14758E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| F/L | rs1415995155 |
-1.348 | 0.822 | N | 0.601 | 0.249 | 0.355450299083 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| F/L | rs1415995155 |
-1.348 | 0.822 | N | 0.601 | 0.249 | 0.355450299083 | gnomAD-4.0.0 | 6.57445E-06 | None | None | None | None | I | None | 2.41278E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.6418 | likely_pathogenic | 0.7147 | pathogenic | -0.942 | Destabilizing | 0.559 | D | 0.627 | neutral | None | None | None | None | I |
| F/C | 0.361 | ambiguous | 0.4121 | ambiguous | -0.412 | Destabilizing | 0.997 | D | 0.723 | prob.delet. | N | 0.432881402 | None | None | I |
| F/D | 0.9036 | likely_pathogenic | 0.9334 | pathogenic | 1.021 | Stabilizing | 0.956 | D | 0.682 | prob.neutral | None | None | None | None | I |
| F/E | 0.9139 | likely_pathogenic | 0.9372 | pathogenic | 1.009 | Stabilizing | 0.956 | D | 0.682 | prob.neutral | None | None | None | None | I |
| F/G | 0.8263 | likely_pathogenic | 0.8727 | pathogenic | -1.137 | Destabilizing | 0.754 | D | 0.695 | prob.neutral | None | None | None | None | I |
| F/H | 0.6099 | likely_pathogenic | 0.6439 | pathogenic | 0.24 | Stabilizing | 0.998 | D | 0.625 | neutral | None | None | None | None | I |
| F/I | 0.4625 | ambiguous | 0.5625 | ambiguous | -0.447 | Destabilizing | 0.97 | D | 0.675 | prob.neutral | N | 0.444135759 | None | None | I |
| F/K | 0.9225 | likely_pathogenic | 0.9408 | pathogenic | -0.058 | Destabilizing | 0.956 | D | 0.684 | prob.neutral | None | None | None | None | I |
| F/L | 0.9002 | likely_pathogenic | 0.9391 | pathogenic | -0.447 | Destabilizing | 0.822 | D | 0.601 | neutral | N | 0.42939838 | None | None | I |
| F/M | 0.6506 | likely_pathogenic | 0.712 | pathogenic | -0.353 | Destabilizing | 0.993 | D | 0.657 | neutral | None | None | None | None | I |
| F/N | 0.7246 | likely_pathogenic | 0.7713 | pathogenic | -0.014 | Destabilizing | 0.956 | D | 0.718 | prob.delet. | None | None | None | None | I |
| F/P | 0.993 | likely_pathogenic | 0.9946 | pathogenic | -0.592 | Destabilizing | 0.978 | D | 0.729 | prob.delet. | None | None | None | None | I |
| F/Q | 0.8212 | likely_pathogenic | 0.8556 | pathogenic | -0.052 | Destabilizing | 0.956 | D | 0.733 | prob.delet. | None | None | None | None | I |
| F/R | 0.8622 | likely_pathogenic | 0.8881 | pathogenic | 0.381 | Stabilizing | 0.956 | D | 0.727 | prob.delet. | None | None | None | None | I |
| F/S | 0.4595 | ambiguous | 0.5477 | ambiguous | -0.767 | Destabilizing | 0.058 | N | 0.519 | neutral | N | 0.291675862 | None | None | I |
| F/T | 0.7446 | likely_pathogenic | 0.7983 | pathogenic | -0.688 | Destabilizing | 0.754 | D | 0.679 | prob.neutral | None | None | None | None | I |
| F/V | 0.4263 | ambiguous | 0.5191 | ambiguous | -0.592 | Destabilizing | 0.822 | D | 0.649 | neutral | N | 0.437593789 | None | None | I |
| F/W | 0.6575 | likely_pathogenic | 0.6939 | pathogenic | -0.163 | Destabilizing | 0.998 | D | 0.681 | prob.neutral | None | None | None | None | I |
| F/Y | 0.1831 | likely_benign | 0.1914 | benign | -0.155 | Destabilizing | 0.966 | D | 0.673 | neutral | N | 0.482000714 | 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.