Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35432 | 106519;106520;106521 | chr2:178530321;178530320;178530319 | chr2:179395048;179395047;179395046 |
| N2AB | 33791 | 101596;101597;101598 | chr2:178530321;178530320;178530319 | chr2:179395048;179395047;179395046 |
| N2A | 32864 | 98815;98816;98817 | chr2:178530321;178530320;178530319 | chr2:179395048;179395047;179395046 |
| N2B | 26367 | 79324;79325;79326 | chr2:178530321;178530320;178530319 | chr2:179395048;179395047;179395046 |
| Novex-1 | 26492 | 79699;79700;79701 | chr2:178530321;178530320;178530319 | chr2:179395048;179395047;179395046 |
| Novex-2 | 26559 | 79900;79901;79902 | chr2:178530321;178530320;178530319 | chr2:179395048;179395047;179395046 |
| 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/F | None | None | 0.371 | N | 0.495 | 0.184 | 0.527098005314 | gnomAD-4.0.0 | 6.84167E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99412E-07 | 0 | 0 |
| S/Y | rs773091136  |
-0.858 | 0.371 | N | 0.498 | 0.22 | 0.551798466036 | gnomAD-2.1.1 | 4.01E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| S/Y | rs773091136 |
-0.858 | 0.371 | N | 0.498 | 0.22 | 0.551798466036 | gnomAD-4.0.0 | 6.84167E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15942E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0868 | likely_benign | 0.0885 | benign | -0.557 | Destabilizing | None | N | 0.165 | neutral | N | 0.460602013 | None | None | N |
| S/C | 0.1883 | likely_benign | 0.1795 | benign | -0.291 | Destabilizing | 0.001 | N | 0.303 | neutral | D | 0.537660074 | None | None | N |
| S/D | 0.3352 | likely_benign | 0.3223 | benign | 0.299 | Stabilizing | 0.052 | N | 0.23 | neutral | None | None | None | None | N |
| S/E | 0.4719 | ambiguous | 0.4552 | ambiguous | 0.202 | Stabilizing | 0.001 | N | 0.212 | neutral | None | None | None | None | N |
| S/F | 0.1579 | likely_benign | 0.1632 | benign | -1.19 | Destabilizing | 0.371 | N | 0.495 | neutral | N | 0.496005453 | None | None | N |
| S/G | 0.1137 | likely_benign | 0.1133 | benign | -0.647 | Destabilizing | 0.043 | N | 0.253 | neutral | None | None | None | None | N |
| S/H | 0.3488 | ambiguous | 0.3436 | ambiguous | -1.216 | Destabilizing | 0.704 | D | 0.399 | neutral | None | None | None | None | N |
| S/I | 0.1414 | likely_benign | 0.1519 | benign | -0.443 | Destabilizing | 0.052 | N | 0.455 | neutral | None | None | None | None | N |
| S/K | 0.578 | likely_pathogenic | 0.59 | pathogenic | -0.346 | Destabilizing | 0.099 | N | 0.22 | neutral | None | None | None | None | N |
| S/L | 0.0954 | likely_benign | 0.0994 | benign | -0.443 | Destabilizing | 0.022 | N | 0.455 | neutral | None | None | None | None | N |
| S/M | 0.2267 | likely_benign | 0.2392 | benign | -0.044 | Destabilizing | 0.438 | N | 0.411 | neutral | None | None | None | None | N |
| S/N | 0.1397 | likely_benign | 0.1374 | benign | -0.052 | Destabilizing | 0.099 | N | 0.299 | neutral | None | None | None | None | N |
| S/P | 0.1953 | likely_benign | 0.2058 | benign | -0.455 | Destabilizing | 0.144 | N | 0.406 | neutral | N | 0.450945167 | None | None | N |
| S/Q | 0.4826 | ambiguous | 0.4777 | ambiguous | -0.361 | Destabilizing | 0.278 | N | 0.314 | neutral | None | None | None | None | N |
| S/R | 0.4839 | ambiguous | 0.477 | ambiguous | -0.186 | Destabilizing | 0.278 | N | 0.403 | neutral | None | None | None | None | N |
| S/T | 0.0805 | likely_benign | 0.0835 | benign | -0.23 | Destabilizing | None | N | 0.181 | neutral | N | 0.455830912 | None | None | N |
| S/V | 0.1694 | likely_benign | 0.1793 | benign | -0.455 | Destabilizing | None | N | 0.327 | neutral | None | None | None | None | N |
| S/W | 0.3556 | ambiguous | 0.3584 | ambiguous | -1.13 | Destabilizing | 0.9 | D | 0.525 | neutral | None | None | None | None | N |
| S/Y | 0.1732 | likely_benign | 0.1716 | benign | -0.866 | Destabilizing | 0.371 | N | 0.498 | neutral | N | 0.496005453 | 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.