Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1098 | 3517;3518;3519 | chr2:178782300;178782299;178782298 | chr2:179647027;179647026;179647025 |
| N2AB | 1098 | 3517;3518;3519 | chr2:178782300;178782299;178782298 | chr2:179647027;179647026;179647025 |
| N2A | 1098 | 3517;3518;3519 | chr2:178782300;178782299;178782298 | chr2:179647027;179647026;179647025 |
| N2B | 1052 | 3379;3380;3381 | chr2:178782300;178782299;178782298 | chr2:179647027;179647026;179647025 |
| Novex-1 | 1052 | 3379;3380;3381 | chr2:178782300;178782299;178782298 | chr2:179647027;179647026;179647025 |
| Novex-2 | 1052 | 3379;3380;3381 | chr2:178782300;178782299;178782298 | chr2:179647027;179647026;179647025 |
| Novex-3 | 1098 | 3517;3518;3519 | chr2:178782300;178782299;178782298 | chr2:179647027;179647026;179647025 |
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/R | rs745660374  |
None | 0.009 | N | 0.227 | 0.149 | 0.0482279557977 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.81E-06 | 0 |
| S/R | rs745660374 |
None | 0.009 | N | 0.227 | 0.149 | 0.0482279557977 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/R | rs745660374 |
None | 0.009 | N | 0.227 | 0.149 | 0.0482279557977 | gnomAD-4.0.0 | 8.05496E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.10169E-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 | 0.1418 | likely_benign | 0.1411 | benign | -0.516 | Destabilizing | 0.207 | N | 0.409 | neutral | None | None | None | None | I |
| S/C | 0.2587 | likely_benign | 0.2516 | benign | -0.337 | Destabilizing | 0.975 | D | 0.478 | neutral | N | 0.461349968 | None | None | I |
| S/D | 0.5037 | ambiguous | 0.5635 | ambiguous | 0.251 | Stabilizing | 0.388 | N | 0.354 | neutral | None | None | None | None | I |
| S/E | 0.541 | ambiguous | 0.5901 | pathogenic | 0.164 | Stabilizing | 0.241 | N | 0.294 | neutral | None | None | None | None | I |
| S/F | 0.392 | ambiguous | 0.4029 | ambiguous | -1.097 | Destabilizing | 0.818 | D | 0.524 | neutral | None | None | None | None | I |
| S/G | 0.1656 | likely_benign | 0.1743 | benign | -0.632 | Destabilizing | 0.001 | N | 0.152 | neutral | N | 0.454791486 | None | None | I |
| S/H | 0.4019 | ambiguous | 0.4394 | ambiguous | -1.186 | Destabilizing | 0.944 | D | 0.461 | neutral | None | None | None | None | I |
| S/I | 0.2677 | likely_benign | 0.2652 | benign | -0.337 | Destabilizing | 0.773 | D | 0.526 | neutral | N | 0.458608357 | None | None | I |
| S/K | 0.6724 | likely_pathogenic | 0.7221 | pathogenic | -0.432 | Destabilizing | 0.002 | N | 0.212 | neutral | None | None | None | None | I |
| S/L | 0.1957 | likely_benign | 0.1976 | benign | -0.337 | Destabilizing | 0.388 | N | 0.42 | neutral | None | None | None | None | I |
| S/M | 0.2813 | likely_benign | 0.2772 | benign | -0.004 | Destabilizing | 0.981 | D | 0.458 | neutral | None | None | None | None | I |
| S/N | 0.1601 | likely_benign | 0.1762 | benign | -0.186 | Destabilizing | 0.324 | N | 0.385 | neutral | N | 0.418559432 | None | None | I |
| S/P | 0.5756 | likely_pathogenic | 0.6262 | pathogenic | -0.369 | Destabilizing | 0.818 | D | 0.451 | neutral | None | None | None | None | I |
| S/Q | 0.4974 | ambiguous | 0.5341 | ambiguous | -0.454 | Destabilizing | 0.69 | D | 0.403 | neutral | None | None | None | None | I |
| S/R | 0.5509 | ambiguous | 0.599 | pathogenic | -0.269 | Destabilizing | 0.009 | N | 0.227 | neutral | N | 0.44958305 | None | None | I |
| S/T | 0.106 | likely_benign | 0.1062 | benign | -0.326 | Destabilizing | 0.324 | N | 0.337 | neutral | N | 0.416691626 | None | None | I |
| S/V | 0.2781 | likely_benign | 0.2795 | benign | -0.369 | Destabilizing | 0.69 | D | 0.455 | neutral | None | None | None | None | I |
| S/W | 0.5821 | likely_pathogenic | 0.5962 | pathogenic | -1.055 | Destabilizing | 0.981 | D | 0.653 | neutral | None | None | None | None | I |
| S/Y | 0.3395 | likely_benign | 0.3628 | ambiguous | -0.787 | Destabilizing | 0.818 | D | 0.526 | 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.