Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 5678 | 17257;17258;17259 | chr2:178731843;178731842;178731841 | chr2:179596570;179596569;179596568 |
| N2AB | 5361 | 16306;16307;16308 | chr2:178731843;178731842;178731841 | chr2:179596570;179596569;179596568 |
| N2A | 4434 | 13525;13526;13527 | chr2:178731843;178731842;178731841 | chr2:179596570;179596569;179596568 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/P | None | None | 0.156 | N | 0.315 | 0.279 | 0.317958651998 | gnomAD-4.0.0 | 6.8421E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.5194E-05 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs374742663  |
-0.109 | 0.992 | N | 0.491 | 0.24 | None | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 8.89E-06 | 0 |
| R/Q | rs374742663 |
-0.109 | 0.992 | N | 0.491 | 0.24 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 1.92753E-04 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/Q | rs374742663 |
-0.109 | 0.992 | N | 0.491 | 0.24 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| R/Q | rs374742663 |
-0.109 | 0.992 | N | 0.491 | 0.24 | None | gnomAD-4.0.0 | 6.19668E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.22876E-05 | None | 0 | 0 | 4.23815E-06 | 4.39194E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.741 | likely_pathogenic | 0.641 | pathogenic | 0.009 | Stabilizing | 0.864 | D | 0.444 | neutral | None | None | None | None | I |
| R/C | 0.34 | likely_benign | 0.302 | benign | -0.362 | Destabilizing | 1.0 | D | 0.455 | neutral | None | None | None | None | I |
| R/D | 0.9046 | likely_pathogenic | 0.8471 | pathogenic | -0.347 | Destabilizing | 0.969 | D | 0.46 | neutral | None | None | None | None | I |
| R/E | 0.7151 | likely_pathogenic | 0.6032 | pathogenic | -0.315 | Destabilizing | 0.969 | D | 0.449 | neutral | None | None | None | None | I |
| R/F | 0.7588 | likely_pathogenic | 0.678 | pathogenic | -0.369 | Destabilizing | 0.999 | D | 0.447 | neutral | None | None | None | None | I |
| R/G | 0.5432 | ambiguous | 0.4509 | ambiguous | -0.103 | Destabilizing | 0.983 | D | 0.487 | neutral | N | 0.495618664 | None | None | I |
| R/H | 0.1577 | likely_benign | 0.1352 | benign | -0.611 | Destabilizing | 0.999 | D | 0.456 | neutral | None | None | None | None | I |
| R/I | 0.5582 | ambiguous | 0.4632 | ambiguous | 0.254 | Stabilizing | 0.995 | D | 0.463 | neutral | None | None | None | None | I |
| R/K | 0.1481 | likely_benign | 0.1315 | benign | -0.265 | Destabilizing | 0.293 | N | 0.271 | neutral | None | None | None | None | I |
| R/L | 0.4731 | ambiguous | 0.4035 | ambiguous | 0.254 | Stabilizing | 0.992 | D | 0.491 | neutral | N | 0.511510836 | None | None | I |
| R/M | 0.6133 | likely_pathogenic | 0.5152 | ambiguous | -0.182 | Destabilizing | 1.0 | D | 0.446 | neutral | None | None | None | None | I |
| R/N | 0.8341 | likely_pathogenic | 0.7634 | pathogenic | -0.249 | Destabilizing | 0.969 | D | 0.454 | neutral | None | None | None | None | I |
| R/P | 0.6125 | likely_pathogenic | 0.5306 | ambiguous | 0.188 | Stabilizing | 0.156 | N | 0.315 | neutral | N | 0.466354549 | None | None | I |
| R/Q | 0.1904 | likely_benign | 0.1589 | benign | -0.244 | Destabilizing | 0.992 | D | 0.491 | neutral | N | 0.489017978 | None | None | I |
| R/S | 0.8031 | likely_pathogenic | 0.719 | pathogenic | -0.371 | Destabilizing | 0.546 | D | 0.281 | neutral | None | None | None | None | I |
| R/T | 0.6324 | likely_pathogenic | 0.5067 | ambiguous | -0.245 | Destabilizing | 0.969 | D | 0.476 | neutral | None | None | None | None | I |
| R/V | 0.6194 | likely_pathogenic | 0.5335 | ambiguous | 0.188 | Stabilizing | 0.995 | D | 0.428 | neutral | None | None | None | None | I |
| R/W | 0.2792 | likely_benign | 0.236 | benign | -0.605 | Destabilizing | 1.0 | D | 0.542 | neutral | None | None | None | None | I |
| R/Y | 0.5529 | ambiguous | 0.4672 | ambiguous | -0.203 | Destabilizing | 0.999 | D | 0.465 | neutral | None | None | 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.