Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29355 | 88288;88289;88290 | chr2:178557091;178557090;178557089 | chr2:179421818;179421817;179421816 |
| N2AB | 27714 | 83365;83366;83367 | chr2:178557091;178557090;178557089 | chr2:179421818;179421817;179421816 |
| N2A | 26787 | 80584;80585;80586 | chr2:178557091;178557090;178557089 | chr2:179421818;179421817;179421816 |
| N2B | 20290 | 61093;61094;61095 | chr2:178557091;178557090;178557089 | chr2:179421818;179421817;179421816 |
| Novex-1 | 20415 | 61468;61469;61470 | chr2:178557091;178557090;178557089 | chr2:179421818;179421817;179421816 |
| Novex-2 | 20482 | 61669;61670;61671 | chr2:178557091;178557090;178557089 | chr2:179421818;179421817;179421816 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/P | rs768443497  |
-0.303 | 0.927 | N | 0.688 | 0.451 | 0.305730143919 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/P | rs768443497 |
-0.303 | 0.927 | N | 0.688 | 0.451 | 0.305730143919 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/P | rs768443497 |
-0.303 | 0.927 | N | 0.688 | 0.451 | 0.305730143919 | gnomAD-4.0.0 | 6.57039E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.46972E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.076 | likely_benign | 0.0725 | benign | -0.769 | Destabilizing | 0.001 | N | 0.139 | neutral | N | 0.50686466 | None | None | N |
| S/C | 0.088 | likely_benign | 0.084 | benign | -0.606 | Destabilizing | 0.944 | D | 0.617 | neutral | None | None | None | None | N |
| S/D | 0.4725 | ambiguous | 0.3768 | ambiguous | -1.129 | Destabilizing | 0.828 | D | 0.507 | neutral | None | None | None | None | N |
| S/E | 0.4577 | ambiguous | 0.3909 | ambiguous | -0.994 | Destabilizing | 0.704 | D | 0.463 | neutral | None | None | None | None | N |
| S/F | 0.1529 | likely_benign | 0.1233 | benign | -0.609 | Destabilizing | 0.007 | N | 0.649 | neutral | None | None | None | None | N |
| S/G | 0.1295 | likely_benign | 0.1242 | benign | -1.129 | Destabilizing | 0.329 | N | 0.335 | neutral | None | None | None | None | N |
| S/H | 0.2549 | likely_benign | 0.2151 | benign | -1.516 | Destabilizing | 0.981 | D | 0.617 | neutral | None | None | None | None | N |
| S/I | 0.1226 | likely_benign | 0.1006 | benign | 0.123 | Stabilizing | 0.329 | N | 0.604 | neutral | None | None | None | None | N |
| S/K | 0.5277 | ambiguous | 0.4483 | ambiguous | -0.479 | Destabilizing | 0.704 | D | 0.459 | neutral | None | None | None | None | N |
| S/L | 0.0785 | likely_benign | 0.0697 | benign | 0.123 | Stabilizing | 0.002 | N | 0.529 | neutral | N | 0.494177663 | None | None | N |
| S/M | 0.1521 | likely_benign | 0.1446 | benign | 0.079 | Stabilizing | 0.893 | D | 0.635 | neutral | None | None | None | None | N |
| S/N | 0.1596 | likely_benign | 0.1379 | benign | -0.919 | Destabilizing | 0.828 | D | 0.509 | neutral | None | None | None | None | N |
| S/P | 0.9296 | likely_pathogenic | 0.8974 | pathogenic | -0.139 | Destabilizing | 0.927 | D | 0.688 | prob.neutral | N | 0.513549366 | None | None | N |
| S/Q | 0.3431 | ambiguous | 0.306 | benign | -0.808 | Destabilizing | 0.944 | D | 0.553 | neutral | None | None | None | None | N |
| S/R | 0.4168 | ambiguous | 0.3475 | ambiguous | -0.682 | Destabilizing | 0.944 | D | 0.685 | prob.neutral | None | None | None | None | N |
| S/T | 0.0774 | likely_benign | 0.0723 | benign | -0.683 | Destabilizing | 0.425 | N | 0.341 | neutral | N | 0.464900607 | None | None | N |
| S/V | 0.1369 | likely_benign | 0.1152 | benign | -0.139 | Destabilizing | 0.013 | N | 0.547 | neutral | None | None | None | None | N |
| S/W | 0.3107 | likely_benign | 0.254 | benign | -0.793 | Destabilizing | 0.995 | D | 0.661 | neutral | None | None | None | None | N |
| S/Y | 0.1588 | likely_benign | 0.1311 | benign | -0.396 | Destabilizing | 0.807 | D | 0.684 | prob.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.