Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14064 | 42415;42416;42417 | chr2:178634591;178634590;178634589 | chr2:179499318;179499317;179499316 |
| N2AB | 12423 | 37492;37493;37494 | chr2:178634591;178634590;178634589 | chr2:179499318;179499317;179499316 |
| N2A | 11496 | 34711;34712;34713 | chr2:178634591;178634590;178634589 | chr2:179499318;179499317;179499316 |
| N2B | 4999 | 15220;15221;15222 | chr2:178634591;178634590;178634589 | chr2:179499318;179499317;179499316 |
| Novex-1 | 5124 | 15595;15596;15597 | chr2:178634591;178634590;178634589 | chr2:179499318;179499317;179499316 |
| Novex-2 | 5191 | 15796;15797;15798 | chr2:178634591;178634590;178634589 | chr2:179499318;179499317;179499316 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs769719800  |
-0.553 | 0.911 | N | 0.443 | 0.199 | 0.32306181527 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| T/A | rs769719800 |
-0.553 | 0.911 | N | 0.443 | 0.199 | 0.32306181527 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| T/A | rs769719800 |
-0.553 | 0.911 | N | 0.443 | 0.199 | 0.32306181527 | gnomAD-4.0.0 | 7.43842E-06 | None | None | None | None | N | None | 2.67201E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 7.63008E-06 | 0 | 1.60179E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1558 | likely_benign | 0.1442 | benign | -0.468 | Destabilizing | 0.911 | D | 0.443 | neutral | N | 0.505424351 | None | None | N |
| T/C | 0.7383 | likely_pathogenic | 0.7043 | pathogenic | -0.383 | Destabilizing | 1.0 | D | 0.525 | neutral | None | None | None | None | N |
| T/D | 0.6423 | likely_pathogenic | 0.6007 | pathogenic | 0.433 | Stabilizing | 0.996 | D | 0.451 | neutral | None | None | None | None | N |
| T/E | 0.4191 | ambiguous | 0.3836 | ambiguous | 0.433 | Stabilizing | 0.985 | D | 0.431 | neutral | None | None | None | None | N |
| T/F | 0.5188 | ambiguous | 0.5023 | ambiguous | -0.708 | Destabilizing | 0.998 | D | 0.594 | neutral | None | None | None | None | N |
| T/G | 0.6579 | likely_pathogenic | 0.6161 | pathogenic | -0.687 | Destabilizing | 0.985 | D | 0.459 | neutral | None | None | None | None | N |
| T/H | 0.5087 | ambiguous | 0.4752 | ambiguous | -0.834 | Destabilizing | 1.0 | D | 0.581 | neutral | None | None | None | None | N |
| T/I | 0.3271 | likely_benign | 0.3067 | benign | 0.008 | Stabilizing | 0.961 | D | 0.426 | neutral | N | 0.512080512 | None | None | N |
| T/K | 0.4315 | ambiguous | 0.403 | ambiguous | -0.278 | Destabilizing | 0.996 | D | 0.451 | neutral | None | None | None | None | N |
| T/L | 0.2291 | likely_benign | 0.2253 | benign | 0.008 | Stabilizing | 0.971 | D | 0.412 | neutral | None | None | None | None | N |
| T/M | 0.1407 | likely_benign | 0.1377 | benign | -0.101 | Destabilizing | 0.999 | D | 0.515 | neutral | None | None | None | None | N |
| T/N | 0.2577 | likely_benign | 0.2219 | benign | -0.297 | Destabilizing | 0.994 | D | 0.413 | neutral | D | 0.561227872 | None | None | N |
| T/P | 0.3942 | ambiguous | 0.4252 | ambiguous | -0.119 | Destabilizing | 0.997 | D | 0.504 | neutral | D | 0.658010738 | None | None | N |
| T/Q | 0.4049 | ambiguous | 0.3716 | ambiguous | -0.356 | Destabilizing | 0.998 | D | 0.509 | neutral | None | None | None | None | N |
| T/R | 0.3733 | ambiguous | 0.3562 | ambiguous | -0.114 | Destabilizing | 0.998 | D | 0.51 | neutral | None | None | None | None | N |
| T/S | 0.2015 | likely_benign | 0.178 | benign | -0.574 | Destabilizing | 0.659 | D | 0.158 | neutral | N | 0.508802964 | None | None | N |
| T/V | 0.2395 | likely_benign | 0.2307 | benign | -0.119 | Destabilizing | 0.469 | N | 0.222 | neutral | None | None | None | None | N |
| T/W | 0.8612 | likely_pathogenic | 0.8582 | pathogenic | -0.733 | Destabilizing | 1.0 | D | 0.653 | neutral | None | None | None | None | N |
| T/Y | 0.5892 | likely_pathogenic | 0.562 | ambiguous | -0.426 | Destabilizing | 0.999 | D | 0.596 | 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.