Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18944 | 57055;57056;57057 | chr2:178598880;178598879;178598878 | chr2:179463607;179463606;179463605 |
| N2AB | 17303 | 52132;52133;52134 | chr2:178598880;178598879;178598878 | chr2:179463607;179463606;179463605 |
| N2A | 16376 | 49351;49352;49353 | chr2:178598880;178598879;178598878 | chr2:179463607;179463606;179463605 |
| N2B | 9879 | 29860;29861;29862 | chr2:178598880;178598879;178598878 | chr2:179463607;179463606;179463605 |
| Novex-1 | 10004 | 30235;30236;30237 | chr2:178598880;178598879;178598878 | chr2:179463607;179463606;179463605 |
| Novex-2 | 10071 | 30436;30437;30438 | chr2:178598880;178598879;178598878 | chr2:179463607;179463606;179463605 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs778351310  |
-0.56 | 1.0 | N | 0.675 | 0.254 | 0.451882325854 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 0 | 0 |
| L/F | rs778351310 |
-0.56 | 1.0 | N | 0.675 | 0.254 | 0.451882325854 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07814E-04 | 0 |
| L/F | rs778351310 |
-0.56 | 1.0 | N | 0.675 | 0.254 | 0.451882325854 | gnomAD-4.0.0 | 6.19929E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 9.88511E-05 | 1.60149E-05 |
| L/S | None | None | 1.0 | N | 0.651 | 0.463 | 0.785456996267 | gnomAD-4.0.0 | 1.59225E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85989E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.297 | likely_benign | 0.2602 | benign | -0.369 | Destabilizing | 0.999 | D | 0.603 | neutral | None | None | None | None | I |
| L/C | 0.6543 | likely_pathogenic | 0.6322 | pathogenic | -0.748 | Destabilizing | 1.0 | D | 0.651 | neutral | None | None | None | None | I |
| L/D | 0.7961 | likely_pathogenic | 0.7557 | pathogenic | -0.205 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | I |
| L/E | 0.5454 | ambiguous | 0.5022 | ambiguous | -0.302 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | I |
| L/F | 0.2106 | likely_benign | 0.2077 | benign | -0.684 | Destabilizing | 1.0 | D | 0.675 | neutral | N | 0.49039091 | None | None | I |
| L/G | 0.5753 | likely_pathogenic | 0.5143 | ambiguous | -0.423 | Destabilizing | 1.0 | D | 0.696 | prob.neutral | None | None | None | None | I |
| L/H | 0.4003 | ambiguous | 0.3923 | ambiguous | 0.035 | Stabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | I |
| L/I | 0.1681 | likely_benign | 0.1497 | benign | -0.34 | Destabilizing | 0.999 | D | 0.473 | neutral | None | None | None | None | I |
| L/K | 0.44 | ambiguous | 0.4161 | ambiguous | -0.266 | Destabilizing | 1.0 | D | 0.651 | neutral | None | None | None | None | I |
| L/M | 0.1344 | likely_benign | 0.1152 | benign | -0.612 | Destabilizing | 1.0 | D | 0.649 | neutral | N | 0.465705897 | None | None | I |
| L/N | 0.5458 | ambiguous | 0.4676 | ambiguous | -0.07 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | I |
| L/P | 0.3774 | ambiguous | 0.3644 | ambiguous | -0.326 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | I |
| L/Q | 0.288 | likely_benign | 0.2568 | benign | -0.239 | Destabilizing | 1.0 | D | 0.653 | neutral | None | None | None | None | I |
| L/R | 0.3244 | likely_benign | 0.3416 | ambiguous | 0.106 | Stabilizing | 1.0 | D | 0.67 | neutral | None | None | None | None | I |
| L/S | 0.4112 | ambiguous | 0.3754 | ambiguous | -0.428 | Destabilizing | 1.0 | D | 0.651 | neutral | N | 0.473130514 | None | None | I |
| L/T | 0.3114 | likely_benign | 0.2605 | benign | -0.437 | Destabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | I |
| L/V | 0.1454 | likely_benign | 0.132 | benign | -0.326 | Destabilizing | 0.999 | D | 0.507 | neutral | N | 0.472650512 | None | None | I |
| L/W | 0.3149 | likely_benign | 0.3592 | ambiguous | -0.706 | Destabilizing | 1.0 | D | 0.69 | prob.neutral | N | 0.475914688 | None | None | I |
| L/Y | 0.4449 | ambiguous | 0.4231 | ambiguous | -0.471 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | 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.