Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23717 | 71374;71375;71376 | chr2:178574983;178574982;178574981 | chr2:179439710;179439709;179439708 |
| N2AB | 22076 | 66451;66452;66453 | chr2:178574983;178574982;178574981 | chr2:179439710;179439709;179439708 |
| N2A | 21149 | 63670;63671;63672 | chr2:178574983;178574982;178574981 | chr2:179439710;179439709;179439708 |
| N2B | 14652 | 44179;44180;44181 | chr2:178574983;178574982;178574981 | chr2:179439710;179439709;179439708 |
| Novex-1 | 14777 | 44554;44555;44556 | chr2:178574983;178574982;178574981 | chr2:179439710;179439709;179439708 |
| Novex-2 | 14844 | 44755;44756;44757 | chr2:178574983;178574982;178574981 | chr2:179439710;179439709;179439708 |
| 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/V | None | None | 0.97 | N | 0.747 | 0.481 | 0.492542987314 | gnomAD-4.0.0 | 1.59237E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43324E-05 | 0 |
| D/Y | rs371818894  |
0.745 | 0.89 | N | 0.785 | 0.352 | None | gnomAD-2.1.1 | 4.3E-05 | None | None | None | None | I | None | 4.14E-05 | 0 | None | 0 | 0 | None | 0 | None | 1.20086E-04 | 5.48E-05 | 1.41123E-04 |
| D/Y | rs371818894 |
0.745 | 0.89 | N | 0.785 | 0.352 | None | gnomAD-3.1.2 | 5.92E-05 | None | None | None | None | I | None | 7.24E-05 | 6.55E-05 | 0 | 0 | 0 | None | 9.42E-05 | 0 | 5.88E-05 | 0 | 0 |
| D/Y | rs371818894 |
0.745 | 0.89 | N | 0.785 | 0.352 | None | gnomAD-4.0.0 | 1.28308E-04 | None | None | None | None | I | None | 3.99936E-05 | 1.667E-05 | None | 0 | 0 | None | 1.09402E-04 | 0 | 1.61073E-04 | 0 | 9.6083E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2418 | likely_benign | 0.2045 | benign | 0.056 | Stabilizing | 0.822 | D | 0.666 | neutral | N | 0.338750238 | None | None | I |
| D/C | 0.7319 | likely_pathogenic | 0.6968 | pathogenic | -0.072 | Destabilizing | 0.998 | D | 0.792 | deleterious | None | None | None | None | I |
| D/E | 0.1978 | likely_benign | 0.182 | benign | -0.225 | Destabilizing | 0.006 | N | 0.207 | neutral | N | 0.390392566 | None | None | I |
| D/F | 0.8449 | likely_pathogenic | 0.7881 | pathogenic | 0.194 | Stabilizing | 0.978 | D | 0.787 | deleterious | None | None | None | None | I |
| D/G | 0.2408 | likely_benign | 0.2077 | benign | -0.127 | Destabilizing | 0.822 | D | 0.571 | neutral | N | 0.401206993 | None | None | I |
| D/H | 0.4868 | ambiguous | 0.4003 | ambiguous | 0.624 | Stabilizing | 0.032 | N | 0.415 | neutral | N | 0.407940964 | None | None | I |
| D/I | 0.6615 | likely_pathogenic | 0.5965 | pathogenic | 0.48 | Stabilizing | 0.978 | D | 0.785 | deleterious | None | None | None | None | I |
| D/K | 0.6001 | likely_pathogenic | 0.5221 | ambiguous | 0.553 | Stabilizing | 0.754 | D | 0.575 | neutral | None | None | None | None | I |
| D/L | 0.6785 | likely_pathogenic | 0.632 | pathogenic | 0.48 | Stabilizing | 0.956 | D | 0.746 | deleterious | None | None | None | None | I |
| D/M | 0.7826 | likely_pathogenic | 0.7443 | pathogenic | 0.288 | Stabilizing | 0.998 | D | 0.765 | deleterious | None | None | None | None | I |
| D/N | 0.155 | likely_benign | 0.1386 | benign | 0.072 | Stabilizing | 0.822 | D | 0.546 | neutral | N | 0.454193329 | None | None | I |
| D/P | 0.897 | likely_pathogenic | 0.8577 | pathogenic | 0.361 | Stabilizing | 0.978 | D | 0.663 | neutral | None | None | None | None | I |
| D/Q | 0.4653 | ambiguous | 0.4177 | ambiguous | 0.137 | Stabilizing | 0.754 | D | 0.564 | neutral | None | None | None | None | I |
| D/R | 0.6571 | likely_pathogenic | 0.5758 | pathogenic | 0.793 | Stabilizing | 0.956 | D | 0.719 | prob.delet. | None | None | None | None | I |
| D/S | 0.1671 | likely_benign | 0.144 | benign | 0.021 | Stabilizing | 0.86 | D | 0.532 | neutral | None | None | None | None | I |
| D/T | 0.3569 | ambiguous | 0.3173 | benign | 0.178 | Stabilizing | 0.86 | D | 0.624 | neutral | None | None | None | None | I |
| D/V | 0.4433 | ambiguous | 0.384 | ambiguous | 0.361 | Stabilizing | 0.97 | D | 0.747 | deleterious | N | 0.375385829 | None | None | I |
| D/W | 0.9559 | likely_pathogenic | 0.9373 | pathogenic | 0.295 | Stabilizing | 0.998 | D | 0.775 | deleterious | None | None | None | None | I |
| D/Y | 0.5134 | ambiguous | 0.4371 | ambiguous | 0.439 | Stabilizing | 0.89 | D | 0.785 | deleterious | N | 0.460639299 | 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.