Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18193 | 54802;54803;54804 | chr2:178604110;178604109;178604108 | chr2:179468837;179468836;179468835 |
| N2AB | 16552 | 49879;49880;49881 | chr2:178604110;178604109;178604108 | chr2:179468837;179468836;179468835 |
| N2A | 15625 | 47098;47099;47100 | chr2:178604110;178604109;178604108 | chr2:179468837;179468836;179468835 |
| N2B | 9128 | 27607;27608;27609 | chr2:178604110;178604109;178604108 | chr2:179468837;179468836;179468835 |
| Novex-1 | 9253 | 27982;27983;27984 | chr2:178604110;178604109;178604108 | chr2:179468837;179468836;179468835 |
| Novex-2 | 9320 | 28183;28184;28185 | chr2:178604110;178604109;178604108 | chr2:179468837;179468836;179468835 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/S | rs777505893  |
-0.556 | 0.489 | N | 0.248 | 0.133 | 0.195762928549 | gnomAD-2.1.1 | 4.03E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-05 | 0 |
| N/S | rs777505893 |
-0.556 | 0.489 | N | 0.248 | 0.133 | 0.195762928549 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| N/S | rs777505893 |
-0.556 | 0.489 | N | 0.248 | 0.133 | 0.195762928549 | gnomAD-4.0.0 | 4.89916E-05 | None | None | None | None | I | None | 1.33622E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 6.36097E-05 | 1.09917E-05 | 3.20461E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.6483 | likely_pathogenic | 0.5371 | ambiguous | -0.619 | Destabilizing | 0.942 | D | 0.615 | neutral | None | None | None | None | I |
| N/C | 0.6957 | likely_pathogenic | 0.6287 | pathogenic | 0.172 | Stabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | I |
| N/D | 0.1362 | likely_benign | 0.1089 | benign | -0.801 | Destabilizing | 0.961 | D | 0.591 | neutral | N | 0.389589198 | None | None | I |
| N/E | 0.8453 | likely_pathogenic | 0.819 | pathogenic | -0.772 | Destabilizing | 0.97 | D | 0.585 | neutral | None | None | None | None | I |
| N/F | 0.9369 | likely_pathogenic | 0.9116 | pathogenic | -0.789 | Destabilizing | 0.999 | D | 0.724 | prob.delet. | None | None | None | None | I |
| N/G | 0.6327 | likely_pathogenic | 0.5254 | ambiguous | -0.88 | Destabilizing | 0.97 | D | 0.583 | neutral | None | None | None | None | I |
| N/H | 0.4528 | ambiguous | 0.395 | ambiguous | -0.937 | Destabilizing | 0.998 | D | 0.606 | neutral | N | 0.519422951 | None | None | I |
| N/I | 0.8301 | likely_pathogenic | 0.7614 | pathogenic | 0.008 | Stabilizing | 0.989 | D | 0.713 | prob.delet. | N | 0.472685458 | None | None | I |
| N/K | 0.9213 | likely_pathogenic | 0.8767 | pathogenic | -0.115 | Destabilizing | 0.961 | D | 0.589 | neutral | N | 0.520980389 | None | None | I |
| N/L | 0.7649 | likely_pathogenic | 0.6991 | pathogenic | 0.008 | Stabilizing | 0.991 | D | 0.645 | neutral | None | None | None | None | I |
| N/M | 0.8482 | likely_pathogenic | 0.7956 | pathogenic | 0.668 | Stabilizing | 1.0 | D | 0.686 | prob.neutral | None | None | None | None | I |
| N/P | 0.8499 | likely_pathogenic | 0.8272 | pathogenic | -0.172 | Destabilizing | 0.996 | D | 0.703 | prob.neutral | None | None | None | None | I |
| N/Q | 0.8416 | likely_pathogenic | 0.8022 | pathogenic | -0.854 | Destabilizing | 0.996 | D | 0.597 | neutral | None | None | None | None | I |
| N/R | 0.8968 | likely_pathogenic | 0.8525 | pathogenic | -0.046 | Destabilizing | 0.996 | D | 0.573 | neutral | None | None | None | None | I |
| N/S | 0.1353 | likely_benign | 0.0991 | benign | -0.571 | Destabilizing | 0.489 | N | 0.248 | neutral | N | 0.467684622 | None | None | I |
| N/T | 0.3692 | ambiguous | 0.2515 | benign | -0.377 | Destabilizing | 0.248 | N | 0.275 | neutral | N | 0.475400028 | None | None | I |
| N/V | 0.7865 | likely_pathogenic | 0.6911 | pathogenic | -0.172 | Destabilizing | 0.991 | D | 0.645 | neutral | None | None | None | None | I |
| N/W | 0.9758 | likely_pathogenic | 0.9701 | pathogenic | -0.647 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | I |
| N/Y | 0.6363 | likely_pathogenic | 0.5694 | pathogenic | -0.383 | Destabilizing | 0.998 | D | 0.704 | prob.neutral | N | 0.502399508 | 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.