Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20101 | 60526;60527;60528 | chr2:178591424;178591423;178591422 | chr2:179456151;179456150;179456149 |
| N2AB | 18460 | 55603;55604;55605 | chr2:178591424;178591423;178591422 | chr2:179456151;179456150;179456149 |
| N2A | 17533 | 52822;52823;52824 | chr2:178591424;178591423;178591422 | chr2:179456151;179456150;179456149 |
| N2B | 11036 | 33331;33332;33333 | chr2:178591424;178591423;178591422 | chr2:179456151;179456150;179456149 |
| Novex-1 | 11161 | 33706;33707;33708 | chr2:178591424;178591423;178591422 | chr2:179456151;179456150;179456149 |
| Novex-2 | 11228 | 33907;33908;33909 | chr2:178591424;178591423;178591422 | chr2:179456151;179456150;179456149 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs777610858  |
-1.128 | 0.98 | N | 0.636 | 0.265 | 0.73577268841 | gnomAD-2.1.1 | 1.1E-05 | None | None | None | None | I | None | 4.15E-05 | 2.92E-05 | None | 0 | 0 | None | 0 | None | 0 | 7.97E-06 | 0 |
| I/T | rs777610858 |
-1.128 | 0.98 | N | 0.636 | 0.265 | 0.73577268841 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs777610858 |
-1.128 | 0.98 | N | 0.636 | 0.265 | 0.73577268841 | gnomAD-4.0.0 | 1.92838E-05 | None | None | None | None | I | None | 2.67845E-05 | 1.68759E-05 | None | 0 | 0 | None | 0 | 0 | 2.03886E-05 | 0 | 6.42963E-05 |
| I/V | rs2050170948 |
None | 0.689 | N | 0.417 | 0.169 | None | gnomAD-4.0.0 | 6.87031E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.01586E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.5287 | ambiguous | 0.5475 | ambiguous | -0.674 | Destabilizing | 0.985 | D | 0.573 | neutral | None | None | None | None | I |
| I/C | 0.8619 | likely_pathogenic | 0.8788 | pathogenic | -0.654 | Destabilizing | 1.0 | D | 0.69 | prob.neutral | None | None | None | None | I |
| I/D | 0.8719 | likely_pathogenic | 0.8795 | pathogenic | 0.033 | Stabilizing | 0.999 | D | 0.715 | prob.delet. | None | None | None | None | I |
| I/E | 0.7759 | likely_pathogenic | 0.7819 | pathogenic | -0.033 | Destabilizing | 0.999 | D | 0.711 | prob.delet. | None | None | None | None | I |
| I/F | 0.2778 | likely_benign | 0.3033 | benign | -0.517 | Destabilizing | 0.151 | N | 0.388 | neutral | N | 0.482014648 | None | None | I |
| I/G | 0.8239 | likely_pathogenic | 0.8401 | pathogenic | -0.869 | Destabilizing | 0.999 | D | 0.709 | prob.delet. | None | None | None | None | I |
| I/H | 0.6898 | likely_pathogenic | 0.7022 | pathogenic | -0.124 | Destabilizing | 1.0 | D | 0.706 | prob.neutral | None | None | None | None | I |
| I/K | 0.5091 | ambiguous | 0.5227 | ambiguous | -0.369 | Destabilizing | 0.999 | D | 0.712 | prob.delet. | None | None | None | None | I |
| I/L | 0.1541 | likely_benign | 0.1712 | benign | -0.27 | Destabilizing | 0.031 | N | 0.185 | neutral | N | 0.4564442 | None | None | I |
| I/M | 0.15 | likely_benign | 0.1579 | benign | -0.404 | Destabilizing | 0.989 | D | 0.579 | neutral | N | 0.468642706 | None | None | I |
| I/N | 0.4619 | ambiguous | 0.4892 | ambiguous | -0.192 | Destabilizing | 0.998 | D | 0.719 | prob.delet. | N | 0.473989811 | None | None | I |
| I/P | 0.9572 | likely_pathogenic | 0.9622 | pathogenic | -0.371 | Destabilizing | 0.999 | D | 0.717 | prob.delet. | None | None | None | None | I |
| I/Q | 0.6274 | likely_pathogenic | 0.6397 | pathogenic | -0.366 | Destabilizing | 0.999 | D | 0.713 | prob.delet. | None | None | None | None | I |
| I/R | 0.4603 | ambiguous | 0.4649 | ambiguous | 0.128 | Stabilizing | 0.999 | D | 0.721 | prob.delet. | None | None | None | None | I |
| I/S | 0.5345 | ambiguous | 0.5545 | ambiguous | -0.703 | Destabilizing | 0.998 | D | 0.683 | prob.neutral | N | 0.459271075 | None | None | I |
| I/T | 0.4347 | ambiguous | 0.4511 | ambiguous | -0.656 | Destabilizing | 0.98 | D | 0.636 | neutral | N | 0.418480458 | None | None | I |
| I/V | 0.0887 | likely_benign | 0.0931 | benign | -0.371 | Destabilizing | 0.689 | D | 0.417 | neutral | N | 0.412538707 | None | None | I |
| I/W | 0.8781 | likely_pathogenic | 0.8871 | pathogenic | -0.539 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | I |
| I/Y | 0.6642 | likely_pathogenic | 0.6902 | pathogenic | -0.299 | Destabilizing | 0.983 | D | 0.675 | 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.