Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30656 | 92191;92192;92193 | chr2:178549756;178549755;178549754 | chr2:179414483;179414482;179414481 |
| N2AB | 29015 | 87268;87269;87270 | chr2:178549756;178549755;178549754 | chr2:179414483;179414482;179414481 |
| N2A | 28088 | 84487;84488;84489 | chr2:178549756;178549755;178549754 | chr2:179414483;179414482;179414481 |
| N2B | 21591 | 64996;64997;64998 | chr2:178549756;178549755;178549754 | chr2:179414483;179414482;179414481 |
| Novex-1 | 21716 | 65371;65372;65373 | chr2:178549756;178549755;178549754 | chr2:179414483;179414482;179414481 |
| Novex-2 | 21783 | 65572;65573;65574 | chr2:178549756;178549755;178549754 | chr2:179414483;179414482;179414481 |
| 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/N | rs775922403  |
-2.597 | 0.295 | N | 0.647 | 0.222 | 0.722529336234 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.87E-06 | 0 |
| I/N | rs775922403 |
-2.597 | 0.295 | N | 0.647 | 0.222 | 0.722529336234 | gnomAD-4.0.0 | 2.05272E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69851E-06 | 0 | 0 |
| I/S | None | None | 0.029 | N | 0.587 | 0.319 | 0.754515611653 | gnomAD-4.0.0 | 1.16321E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.4392E-05 | 0 | 1.65662E-05 |
| I/V | rs886043632 |
None | None | N | 0.151 | 0.069 | 0.352048277211 | gnomAD-4.0.0 | 1.59144E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02425E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3057 | likely_benign | 0.3702 | ambiguous | -2.64 | Highly Destabilizing | 0.007 | N | 0.529 | neutral | None | None | None | None | N |
| I/C | 0.4808 | ambiguous | 0.5369 | ambiguous | -1.76 | Destabilizing | 0.356 | N | 0.619 | neutral | None | None | None | None | N |
| I/D | 0.7538 | likely_pathogenic | 0.832 | pathogenic | -3.056 | Highly Destabilizing | 0.136 | N | 0.65 | neutral | None | None | None | None | N |
| I/E | 0.5413 | ambiguous | 0.6373 | pathogenic | -2.9 | Highly Destabilizing | 0.136 | N | 0.627 | neutral | None | None | None | None | N |
| I/F | 0.1826 | likely_benign | 0.2471 | benign | -1.657 | Destabilizing | 0.029 | N | 0.533 | neutral | N | 0.479989612 | None | None | N |
| I/G | 0.6498 | likely_pathogenic | 0.7197 | pathogenic | -3.104 | Highly Destabilizing | 0.136 | N | 0.626 | neutral | None | None | None | None | N |
| I/H | 0.3825 | ambiguous | 0.4397 | ambiguous | -2.509 | Highly Destabilizing | 0.864 | D | 0.627 | neutral | None | None | None | None | N |
| I/K | 0.2563 | likely_benign | 0.3274 | benign | -2.097 | Highly Destabilizing | 0.072 | N | 0.619 | neutral | None | None | None | None | N |
| I/L | 0.0881 | likely_benign | 0.1171 | benign | -1.317 | Destabilizing | None | N | 0.155 | neutral | N | 0.497103452 | None | None | N |
| I/M | 0.0856 | likely_benign | 0.1109 | benign | -1.089 | Destabilizing | 0.001 | N | 0.334 | neutral | N | 0.496550157 | None | None | N |
| I/N | 0.2551 | likely_benign | 0.3074 | benign | -2.27 | Highly Destabilizing | 0.295 | N | 0.647 | neutral | N | 0.463402613 | None | None | N |
| I/P | 0.973 | likely_pathogenic | 0.9811 | pathogenic | -1.739 | Destabilizing | 0.628 | D | 0.643 | neutral | None | None | None | None | N |
| I/Q | 0.3165 | likely_benign | 0.3769 | ambiguous | -2.253 | Highly Destabilizing | 0.214 | N | 0.653 | neutral | None | None | None | None | N |
| I/R | 0.1985 | likely_benign | 0.2552 | benign | -1.591 | Destabilizing | 0.214 | N | 0.648 | neutral | None | None | None | None | N |
| I/S | 0.2676 | likely_benign | 0.3079 | benign | -2.876 | Highly Destabilizing | 0.029 | N | 0.587 | neutral | N | 0.478264411 | None | None | N |
| I/T | 0.1451 | likely_benign | 0.1546 | benign | -2.606 | Highly Destabilizing | None | N | 0.395 | neutral | N | 0.477632257 | None | None | N |
| I/V | 0.0593 | likely_benign | 0.0594 | benign | -1.739 | Destabilizing | None | N | 0.151 | neutral | N | 0.435228274 | None | None | N |
| I/W | 0.7537 | likely_pathogenic | 0.8207 | pathogenic | -2.061 | Highly Destabilizing | 0.864 | D | 0.645 | neutral | None | None | None | None | N |
| I/Y | 0.462 | ambiguous | 0.5184 | ambiguous | -1.832 | Destabilizing | 0.356 | N | 0.643 | 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.