Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14561 | 43906;43907;43908 | chr2:178632213;178632212;178632211 | chr2:179496940;179496939;179496938 |
| N2AB | 12920 | 38983;38984;38985 | chr2:178632213;178632212;178632211 | chr2:179496940;179496939;179496938 |
| N2A | 11993 | 36202;36203;36204 | chr2:178632213;178632212;178632211 | chr2:179496940;179496939;179496938 |
| N2B | 5496 | 16711;16712;16713 | chr2:178632213;178632212;178632211 | chr2:179496940;179496939;179496938 |
| Novex-1 | 5621 | 17086;17087;17088 | chr2:178632213;178632212;178632211 | chr2:179496940;179496939;179496938 |
| Novex-2 | 5688 | 17287;17288;17289 | chr2:178632213;178632212;178632211 | chr2:179496940;179496939;179496938 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | None | None | 1.0 | D | 0.67 | 0.673 | 0.621717555292 | gnomAD-4.0.0 | 1.60532E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.45518E-05 | 0 |
| D/G | None | None | 1.0 | D | 0.632 | 0.722 | 0.613699239204 | gnomAD-4.0.0 | 1.60532E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.89243E-05 | 0 | 0 | 0 | 0 |
| D/Y | rs745655055  |
-0.023 | 1.0 | D | 0.691 | 0.651 | 0.641141256235 | gnomAD-2.1.1 | 7.4E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.62E-05 | 0 |
| D/Y | rs745655055 |
-0.023 | 1.0 | D | 0.691 | 0.651 | 0.641141256235 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/Y | rs745655055 |
-0.023 | 1.0 | D | 0.691 | 0.651 | 0.641141256235 | gnomAD-4.0.0 | 4.97547E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.79717E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.208 | likely_benign | 0.1766 | benign | -0.074 | Destabilizing | 1.0 | D | 0.67 | neutral | D | 0.607283674 | None | None | N |
| D/C | 0.7298 | likely_pathogenic | 0.704 | pathogenic | 0.082 | Stabilizing | 1.0 | D | 0.71 | prob.delet. | None | None | None | None | N |
| D/E | 0.2058 | likely_benign | 0.1567 | benign | -0.215 | Destabilizing | 1.0 | D | 0.443 | neutral | D | 0.533590941 | None | None | N |
| D/F | 0.6355 | likely_pathogenic | 0.5927 | pathogenic | -0.141 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| D/G | 0.1682 | likely_benign | 0.1521 | benign | -0.203 | Destabilizing | 1.0 | D | 0.632 | neutral | D | 0.686130472 | None | None | N |
| D/H | 0.3153 | likely_benign | 0.2836 | benign | 0.271 | Stabilizing | 1.0 | D | 0.619 | neutral | D | 0.685174385 | None | None | N |
| D/I | 0.5136 | ambiguous | 0.4561 | ambiguous | 0.202 | Stabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | N |
| D/K | 0.3788 | ambiguous | 0.3268 | benign | 0.568 | Stabilizing | 1.0 | D | 0.653 | neutral | None | None | None | None | N |
| D/L | 0.4785 | ambiguous | 0.442 | ambiguous | 0.202 | Stabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | N |
| D/M | 0.7351 | likely_pathogenic | 0.6881 | pathogenic | 0.192 | Stabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | N |
| D/N | 0.1145 | likely_benign | 0.1032 | benign | 0.279 | Stabilizing | 1.0 | D | 0.609 | neutral | D | 0.64778899 | None | None | N |
| D/P | 0.8005 | likely_pathogenic | 0.7636 | pathogenic | 0.13 | Stabilizing | 1.0 | D | 0.649 | neutral | None | None | None | None | N |
| D/Q | 0.4252 | ambiguous | 0.3578 | ambiguous | 0.295 | Stabilizing | 1.0 | D | 0.66 | neutral | None | None | None | None | N |
| D/R | 0.3855 | ambiguous | 0.3576 | ambiguous | 0.694 | Stabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| D/S | 0.1433 | likely_benign | 0.1208 | benign | 0.207 | Stabilizing | 1.0 | D | 0.638 | neutral | None | None | None | None | N |
| D/T | 0.3005 | likely_benign | 0.2617 | benign | 0.316 | Stabilizing | 1.0 | D | 0.654 | neutral | None | None | None | None | N |
| D/V | 0.3211 | likely_benign | 0.2906 | benign | 0.13 | Stabilizing | 1.0 | D | 0.723 | prob.delet. | D | 0.684583142 | None | None | N |
| D/W | 0.8797 | likely_pathogenic | 0.868 | pathogenic | -0.075 | Destabilizing | 1.0 | D | 0.714 | prob.delet. | None | None | None | None | N |
| D/Y | 0.2499 | likely_benign | 0.2451 | benign | 0.089 | Stabilizing | 1.0 | D | 0.691 | prob.neutral | D | 0.684583143 | 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.