Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19227 | 57904;57905;57906 | chr2:178595675;178595674;178595673 | chr2:179460402;179460401;179460400 |
| N2AB | 17586 | 52981;52982;52983 | chr2:178595675;178595674;178595673 | chr2:179460402;179460401;179460400 |
| N2A | 16659 | 50200;50201;50202 | chr2:178595675;178595674;178595673 | chr2:179460402;179460401;179460400 |
| N2B | 10162 | 30709;30710;30711 | chr2:178595675;178595674;178595673 | chr2:179460402;179460401;179460400 |
| Novex-1 | 10287 | 31084;31085;31086 | chr2:178595675;178595674;178595673 | chr2:179460402;179460401;179460400 |
| Novex-2 | 10354 | 31285;31286;31287 | chr2:178595675;178595674;178595673 | chr2:179460402;179460401;179460400 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs1440846373  |
-0.111 | 1.0 | N | 0.394 | 0.203 | 0.177238962908 | gnomAD-2.1.1 | 4.16E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.2E-06 | 0 |
| D/E | rs1440846373 |
-0.111 | 1.0 | N | 0.394 | 0.203 | 0.177238962908 | gnomAD-4.0.0 | 6.86601E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.01297E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2678 | likely_benign | 0.3035 | benign | -0.129 | Destabilizing | 1.0 | D | 0.627 | neutral | N | 0.477771117 | None | None | N |
| D/C | 0.6806 | likely_pathogenic | 0.7626 | pathogenic | 0.069 | Stabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | N |
| D/E | 0.1852 | likely_benign | 0.1706 | benign | -0.299 | Destabilizing | 1.0 | D | 0.394 | neutral | N | 0.434902987 | None | None | N |
| D/F | 0.738 | likely_pathogenic | 0.7997 | pathogenic | -0.188 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | N |
| D/G | 0.2269 | likely_benign | 0.2661 | benign | -0.272 | Destabilizing | 1.0 | D | 0.537 | neutral | N | 0.423125768 | None | None | N |
| D/H | 0.4094 | ambiguous | 0.5297 | ambiguous | 0.171 | Stabilizing | 1.0 | D | 0.593 | neutral | N | 0.490777699 | None | None | N |
| D/I | 0.5575 | ambiguous | 0.6208 | pathogenic | 0.184 | Stabilizing | 1.0 | D | 0.692 | prob.neutral | None | None | None | None | N |
| D/K | 0.5879 | likely_pathogenic | 0.6707 | pathogenic | 0.501 | Stabilizing | 1.0 | D | 0.59 | neutral | None | None | None | None | N |
| D/L | 0.513 | ambiguous | 0.5828 | pathogenic | 0.184 | Stabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| D/M | 0.737 | likely_pathogenic | 0.7707 | pathogenic | 0.209 | Stabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| D/N | 0.134 | likely_benign | 0.1658 | benign | 0.222 | Stabilizing | 1.0 | D | 0.525 | neutral | N | 0.46478039 | None | None | N |
| D/P | 0.8508 | likely_pathogenic | 0.8696 | pathogenic | 0.1 | Stabilizing | 1.0 | D | 0.597 | neutral | None | None | None | None | N |
| D/Q | 0.4628 | ambiguous | 0.523 | ambiguous | 0.226 | Stabilizing | 1.0 | D | 0.585 | neutral | None | None | None | None | N |
| D/R | 0.6199 | likely_pathogenic | 0.7056 | pathogenic | 0.644 | Stabilizing | 1.0 | D | 0.657 | neutral | None | None | None | None | N |
| D/S | 0.1636 | likely_benign | 0.1932 | benign | 0.144 | Stabilizing | 1.0 | D | 0.537 | neutral | None | None | None | None | N |
| D/T | 0.2898 | likely_benign | 0.3332 | benign | 0.258 | Stabilizing | 1.0 | D | 0.594 | neutral | None | None | None | None | N |
| D/V | 0.3697 | ambiguous | 0.4241 | ambiguous | 0.1 | Stabilizing | 1.0 | D | 0.698 | prob.neutral | N | 0.476154964 | None | None | N |
| D/W | 0.9272 | likely_pathogenic | 0.9497 | pathogenic | -0.107 | Destabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | N |
| D/Y | 0.4114 | ambiguous | 0.5065 | ambiguous | 0.045 | Stabilizing | 1.0 | D | 0.675 | neutral | N | 0.515732072 | 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.