Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20587 | 61984;61985;61986 | chr2:178589966;178589965;178589964 | chr2:179454693;179454692;179454691 |
| N2AB | 18946 | 57061;57062;57063 | chr2:178589966;178589965;178589964 | chr2:179454693;179454692;179454691 |
| N2A | 18019 | 54280;54281;54282 | chr2:178589966;178589965;178589964 | chr2:179454693;179454692;179454691 |
| N2B | 11522 | 34789;34790;34791 | chr2:178589966;178589965;178589964 | chr2:179454693;179454692;179454691 |
| Novex-1 | 11647 | 35164;35165;35166 | chr2:178589966;178589965;178589964 | chr2:179454693;179454692;179454691 |
| Novex-2 | 11714 | 35365;35366;35367 | chr2:178589966;178589965;178589964 | chr2:179454693;179454692;179454691 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs757267029  |
None | 0.27 | N | 0.417 | 0.221 | 0.330331372229 | gnomAD-4.0.0 | 1.59262E-06 | None | None | None | None | N | None | 0 | 2.28959E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/K | None | -0.773 | 0.642 | N | 0.506 | 0.264 | 0.351180957027 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| T/K | None | -0.773 | 0.642 | N | 0.506 | 0.264 | 0.351180957027 | gnomAD-4.0.0 | 4.77786E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86002E-06 | 1.43308E-05 | 3.02718E-05 |
| T/R | rs757267029 |
-0.582 | 0.784 | D | 0.597 | 0.294 | 0.539879176108 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 9.19118E-04 |
| T/R | rs757267029 |
-0.582 | 0.784 | D | 0.597 | 0.294 | 0.539879176108 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| T/R | rs757267029 |
-0.582 | 0.784 | D | 0.597 | 0.294 | 0.539879176108 | gnomAD-4.0.0 | 6.57704E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47141E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1157 | likely_benign | 0.1235 | benign | -0.862 | Destabilizing | 0.139 | N | 0.307 | neutral | N | 0.497895673 | None | None | N |
| T/C | 0.4324 | ambiguous | 0.4282 | ambiguous | -0.756 | Destabilizing | 0.981 | D | 0.564 | neutral | None | None | None | None | N |
| T/D | 0.6396 | likely_pathogenic | 0.6028 | pathogenic | -1.249 | Destabilizing | 0.936 | D | 0.558 | neutral | None | None | None | None | N |
| T/E | 0.526 | ambiguous | 0.4832 | ambiguous | -1.195 | Destabilizing | 0.828 | D | 0.497 | neutral | None | None | None | None | N |
| T/F | 0.2421 | likely_benign | 0.2827 | benign | -0.828 | Destabilizing | 0.704 | D | 0.581 | neutral | None | None | None | None | N |
| T/G | 0.3808 | ambiguous | 0.4077 | ambiguous | -1.165 | Destabilizing | 0.828 | D | 0.514 | neutral | None | None | None | None | N |
| T/H | 0.3453 | ambiguous | 0.352 | ambiguous | -1.482 | Destabilizing | 0.981 | D | 0.559 | neutral | None | None | None | None | N |
| T/I | 0.1498 | likely_benign | 0.1641 | benign | -0.128 | Destabilizing | 0.27 | N | 0.417 | neutral | N | 0.517732227 | None | None | N |
| T/K | 0.4839 | ambiguous | 0.4377 | ambiguous | -0.895 | Destabilizing | 0.642 | D | 0.506 | neutral | N | 0.478136476 | None | None | N |
| T/L | 0.102 | likely_benign | 0.1133 | benign | -0.128 | Destabilizing | 0.031 | N | 0.37 | neutral | None | None | None | None | N |
| T/M | 0.0844 | likely_benign | 0.0981 | benign | 0.159 | Stabilizing | 0.037 | N | 0.358 | neutral | None | None | None | None | N |
| T/N | 0.1662 | likely_benign | 0.1799 | benign | -1.129 | Destabilizing | 0.936 | D | 0.525 | neutral | None | None | None | None | N |
| T/P | 0.7297 | likely_pathogenic | 0.6204 | pathogenic | -0.34 | Destabilizing | 0.917 | D | 0.593 | neutral | N | 0.488084369 | None | None | N |
| T/Q | 0.3257 | likely_benign | 0.3257 | benign | -1.268 | Destabilizing | 0.944 | D | 0.587 | neutral | None | None | None | None | N |
| T/R | 0.4158 | ambiguous | 0.3652 | ambiguous | -0.702 | Destabilizing | 0.784 | D | 0.597 | neutral | D | 0.524484841 | None | None | N |
| T/S | 0.1332 | likely_benign | 0.1498 | benign | -1.287 | Destabilizing | 0.6 | D | 0.387 | neutral | N | 0.490313553 | None | None | N |
| T/V | 0.1112 | likely_benign | 0.128 | benign | -0.34 | Destabilizing | 0.001 | N | 0.235 | neutral | None | None | None | None | N |
| T/W | 0.6175 | likely_pathogenic | 0.6255 | pathogenic | -0.847 | Destabilizing | 0.995 | D | 0.572 | neutral | None | None | None | None | N |
| T/Y | 0.2752 | likely_benign | 0.2994 | benign | -0.555 | Destabilizing | 0.944 | D | 0.565 | 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.