Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15071 | 45436;45437;45438 | chr2:178621613;178621612;178621611 | chr2:179486340;179486339;179486338 |
| N2AB | 13430 | 40513;40514;40515 | chr2:178621613;178621612;178621611 | chr2:179486340;179486339;179486338 |
| N2A | 12503 | 37732;37733;37734 | chr2:178621613;178621612;178621611 | chr2:179486340;179486339;179486338 |
| N2B | 6006 | 18241;18242;18243 | chr2:178621613;178621612;178621611 | chr2:179486340;179486339;179486338 |
| Novex-1 | 6131 | 18616;18617;18618 | chr2:178621613;178621612;178621611 | chr2:179486340;179486339;179486338 |
| Novex-2 | 6198 | 18817;18818;18819 | chr2:178621613;178621612;178621611 | chr2:179486340;179486339;179486338 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs184078045  |
-0.645 | 0.425 | N | 0.349 | 0.286 | None | gnomAD-2.1.1 | 6.81E-05 | None | None | None | None | N | None | 4.14E-05 | 2.84E-05 | None | 0 | 8.79371E-04 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs184078045 |
-0.645 | 0.425 | N | 0.349 | 0.286 | None | gnomAD-3.1.2 | 6.59E-05 | None | None | None | None | N | None | 7.25E-05 | 0 | 0 | 0 | 1.17233E-03 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs184078045 |
-0.645 | 0.425 | N | 0.349 | 0.286 | None | 1000 genomes | 7.98722E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 4E-03 | 0 | None | None | None | 0 | None |
| I/T | rs184078045 |
-0.645 | 0.425 | N | 0.349 | 0.286 | None | gnomAD-4.0.0 | 2.54265E-05 | None | None | None | None | N | None | 5.33988E-05 | 3.34146E-05 | None | 0 | 5.59635E-04 | None | 1.56274E-05 | 0 | 5.08863E-06 | 1.09832E-05 | 3.20492E-05 |
| I/V | rs1441511907 |
-0.237 | 0.396 | N | 0.189 | 0.163 | 0.486636631601 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.95E-06 | 0 |
| I/V | rs1441511907 |
-0.237 | 0.396 | N | 0.189 | 0.163 | 0.486636631601 | gnomAD-4.0.0 | 6.37462E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.58802E-06 | 0 | 3.0303E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.1227 | likely_benign | 0.1293 | benign | -0.552 | Destabilizing | 0.495 | N | 0.297 | neutral | None | None | None | None | N |
| I/C | 0.5421 | ambiguous | 0.6335 | pathogenic | -0.763 | Destabilizing | 0.995 | D | 0.351 | neutral | None | None | None | None | N |
| I/D | 0.3643 | ambiguous | 0.3716 | ambiguous | -0.438 | Destabilizing | 0.828 | D | 0.416 | neutral | None | None | None | None | N |
| I/E | 0.2358 | likely_benign | 0.2472 | benign | -0.518 | Destabilizing | 0.704 | D | 0.423 | neutral | None | None | None | None | N |
| I/F | 0.1372 | likely_benign | 0.1281 | benign | -0.599 | Destabilizing | 0.975 | D | 0.295 | neutral | N | 0.506715774 | None | None | N |
| I/G | 0.3353 | likely_benign | 0.3531 | ambiguous | -0.69 | Destabilizing | 0.704 | D | 0.405 | neutral | None | None | None | None | N |
| I/H | 0.2596 | likely_benign | 0.2874 | benign | 0.027 | Stabilizing | 0.981 | D | 0.371 | neutral | None | None | None | None | N |
| I/K | 0.1352 | likely_benign | 0.1489 | benign | -0.462 | Destabilizing | 0.704 | D | 0.419 | neutral | None | None | None | None | N |
| I/L | 0.0919 | likely_benign | 0.0939 | benign | -0.304 | Destabilizing | 0.244 | N | 0.167 | neutral | N | 0.483544074 | None | None | N |
| I/M | 0.0824 | likely_benign | 0.0808 | benign | -0.589 | Destabilizing | 0.975 | D | 0.327 | neutral | N | 0.509288434 | None | None | N |
| I/N | 0.1499 | likely_benign | 0.1464 | benign | -0.346 | Destabilizing | 0.927 | D | 0.418 | neutral | N | 0.457414292 | None | None | N |
| I/P | 0.2893 | likely_benign | 0.283 | benign | -0.357 | Destabilizing | 0.001 | N | 0.21 | neutral | None | None | None | None | N |
| I/Q | 0.1604 | likely_benign | 0.1901 | benign | -0.531 | Destabilizing | 0.944 | D | 0.41 | neutral | None | None | None | None | N |
| I/R | 0.1003 | likely_benign | 0.1098 | benign | 0.056 | Stabilizing | 0.944 | D | 0.414 | neutral | None | None | None | None | N |
| I/S | 0.1221 | likely_benign | 0.1273 | benign | -0.712 | Destabilizing | 0.642 | D | 0.389 | neutral | N | 0.45871117 | None | None | N |
| I/T | 0.0753 | likely_benign | 0.0709 | benign | -0.689 | Destabilizing | 0.425 | N | 0.349 | neutral | N | 0.407427296 | None | None | N |
| I/V | 0.0825 | likely_benign | 0.0813 | benign | -0.357 | Destabilizing | 0.396 | N | 0.189 | neutral | N | 0.475168206 | None | None | N |
| I/W | 0.5256 | ambiguous | 0.5475 | ambiguous | -0.634 | Destabilizing | 0.995 | D | 0.398 | neutral | None | None | None | None | N |
| I/Y | 0.3747 | ambiguous | 0.4032 | ambiguous | -0.398 | Destabilizing | 0.981 | D | 0.369 | 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.