Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32292 | 97099;97100;97101 | chr2:178543099;178543098;178543097 | chr2:179407826;179407825;179407824 |
| N2AB | 30651 | 92176;92177;92178 | chr2:178543099;178543098;178543097 | chr2:179407826;179407825;179407824 |
| N2A | 29724 | 89395;89396;89397 | chr2:178543099;178543098;178543097 | chr2:179407826;179407825;179407824 |
| N2B | 23227 | 69904;69905;69906 | chr2:178543099;178543098;178543097 | chr2:179407826;179407825;179407824 |
| Novex-1 | 23352 | 70279;70280;70281 | chr2:178543099;178543098;178543097 | chr2:179407826;179407825;179407824 |
| Novex-2 | 23419 | 70480;70481;70482 | chr2:178543099;178543098;178543097 | chr2:179407826;179407825;179407824 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/I | rs746347387  |
-0.016 | 0.004 | N | 0.363 | 0.053 | 0.48286525802 | gnomAD-2.1.1 | 1.22E-05 | None | None | None | None | N | None | 0 | 5.82E-05 | None | 0 | 0 | None | 0 | None | 0 | 8.97E-06 | 0 |
| V/I | rs746347387 |
-0.016 | 0.004 | N | 0.363 | 0.053 | 0.48286525802 | gnomAD-3.1.2 | 6.64E-06 | None | None | None | None | N | None | 0 | 6.63E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs746347387 |
-0.016 | 0.004 | N | 0.363 | 0.053 | 0.48286525802 | gnomAD-4.0.0 | 2.74561E-05 | None | None | None | None | N | None | 0 | 5.0366E-05 | None | 0 | 0 | None | 0 | 0 | 3.32562E-05 | 0 | 3.22508E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1323 | likely_benign | 0.1247 | benign | -0.482 | Destabilizing | 0.546 | D | 0.597 | neutral | N | 0.454718112 | None | None | N |
| V/C | 0.6953 | likely_pathogenic | 0.664 | pathogenic | -0.961 | Destabilizing | 0.992 | D | 0.633 | neutral | None | None | None | None | N |
| V/D | 0.2931 | likely_benign | 0.2936 | benign | -0.383 | Destabilizing | 0.963 | D | 0.711 | prob.delet. | N | 0.482502146 | None | None | N |
| V/E | 0.2773 | likely_benign | 0.2761 | benign | -0.489 | Destabilizing | 0.972 | D | 0.591 | neutral | None | None | None | None | N |
| V/F | 0.1567 | likely_benign | 0.149 | benign | -0.863 | Destabilizing | 0.808 | D | 0.597 | neutral | N | 0.468468722 | None | None | N |
| V/G | 0.1364 | likely_benign | 0.1376 | benign | -0.511 | Destabilizing | 0.895 | D | 0.637 | neutral | N | 0.474517381 | None | None | N |
| V/H | 0.5312 | ambiguous | 0.5034 | ambiguous | -0.155 | Destabilizing | 0.992 | D | 0.729 | deleterious | None | None | None | None | N |
| V/I | 0.085 | likely_benign | 0.0787 | benign | -0.527 | Destabilizing | 0.004 | N | 0.363 | neutral | N | 0.491292201 | None | None | N |
| V/K | 0.3399 | likely_benign | 0.3506 | ambiguous | -0.508 | Destabilizing | 0.919 | D | 0.573 | neutral | None | None | None | None | N |
| V/L | 0.1434 | likely_benign | 0.1298 | benign | -0.527 | Destabilizing | 0.004 | N | 0.337 | neutral | N | 0.445693197 | None | None | N |
| V/M | 0.1102 | likely_benign | 0.1022 | benign | -0.757 | Destabilizing | 0.248 | N | 0.463 | neutral | None | None | None | None | N |
| V/N | 0.2157 | likely_benign | 0.2063 | benign | -0.335 | Destabilizing | 0.972 | D | 0.697 | prob.delet. | None | None | None | None | N |
| V/P | 0.2891 | likely_benign | 0.2859 | benign | -0.49 | Destabilizing | 0.972 | D | 0.657 | prob.neutral | None | None | None | None | N |
| V/Q | 0.2952 | likely_benign | 0.2855 | benign | -0.508 | Destabilizing | 0.919 | D | 0.651 | prob.neutral | None | None | None | None | N |
| V/R | 0.2922 | likely_benign | 0.3107 | benign | -0.123 | Destabilizing | 0.919 | D | 0.7 | prob.delet. | None | None | None | None | N |
| V/S | 0.1533 | likely_benign | 0.1491 | benign | -0.651 | Destabilizing | 0.919 | D | 0.555 | neutral | None | None | None | None | N |
| V/T | 0.1637 | likely_benign | 0.1494 | benign | -0.675 | Destabilizing | 0.615 | D | 0.631 | neutral | None | None | None | None | N |
| V/W | 0.7382 | likely_pathogenic | 0.7309 | pathogenic | -0.891 | Destabilizing | 0.992 | D | 0.734 | deleterious | None | None | None | None | N |
| V/Y | 0.4884 | ambiguous | 0.4746 | ambiguous | -0.666 | Destabilizing | 0.919 | D | 0.615 | 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.