Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 8540 | 25843;25844;25845 | chr2:178717116;178717115;178717114 | chr2:179581843;179581842;179581841 |
| N2AB | 8223 | 24892;24893;24894 | chr2:178717116;178717115;178717114 | chr2:179581843;179581842;179581841 |
| N2A | 7296 | 22111;22112;22113 | chr2:178717116;178717115;178717114 | chr2:179581843;179581842;179581841 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | rs77120780  |
-0.176 | None | N | 0.145 | 0.153 | 0.162503812791 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/A | rs77120780 |
-0.176 | None | N | 0.145 | 0.153 | 0.162503812791 | gnomAD-4.0.0 | 1.59295E-06 | None | None | None | None | I | None | 0 | 2.28718E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/F | rs201523784 |
-0.895 | None | N | 0.354 | 0.342 | None | gnomAD-2.1.1 | 5.36569E-04 | None | None | None | None | I | None | 8.27E-05 | 4.81559E-04 | None | 3.9721E-03 | 0 | None | 2.61832E-04 | None | 4.02E-05 | 6.10902E-04 | 4.22654E-04 |
| S/F | rs201523784 |
-0.895 | None | N | 0.354 | 0.342 | None | gnomAD-3.1.2 | 4.27148E-04 | None | None | None | None | I | None | 1.92957E-04 | 1.96464E-04 | 0 | 2.88184E-03 | 0 | None | 9.41E-05 | 0 | 5.73378E-04 | 8.27815E-04 | 0 |
| S/F | rs201523784 |
-0.895 | None | N | 0.354 | 0.342 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| S/F | rs201523784 |
-0.895 | None | N | 0.354 | 0.342 | None | gnomAD-4.0.0 | 6.03203E-04 | None | None | None | None | I | None | 1.33319E-04 | 4.00027E-04 | None | 3.92343E-03 | 0 | None | 1.09419E-04 | 0 | 6.35127E-04 | 1.97863E-04 | 7.84753E-04 |
| S/Y | None | None | 0.001 | N | 0.428 | 0.273 | 0.496165130923 | gnomAD-4.0.0 | 6.84575E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.16093E-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 | 0.0789 | benign | -0.537 | Destabilizing | None | N | 0.145 | neutral | N | 0.489442219 | None | None | I |
| S/C | 0.175 | likely_benign | 0.1598 | benign | -0.31 | Destabilizing | 0.629 | D | 0.547 | neutral | D | 0.522754348 | None | None | I |
| S/D | 0.4669 | ambiguous | 0.4321 | ambiguous | -0.268 | Destabilizing | 0.04 | N | 0.387 | neutral | None | None | None | None | I |
| S/E | 0.5298 | ambiguous | 0.4862 | ambiguous | -0.332 | Destabilizing | 0.105 | N | 0.355 | neutral | None | None | None | None | I |
| S/F | 0.1459 | likely_benign | 0.1265 | benign | -0.968 | Destabilizing | None | N | 0.354 | neutral | N | 0.511398043 | None | None | I |
| S/G | 0.1189 | likely_benign | 0.1118 | benign | -0.711 | Destabilizing | 0.031 | N | 0.341 | neutral | None | None | None | None | I |
| S/H | 0.3252 | likely_benign | 0.3063 | benign | -1.272 | Destabilizing | 0.523 | D | 0.556 | neutral | None | None | None | None | I |
| S/I | 0.134 | likely_benign | 0.1284 | benign | -0.196 | Destabilizing | 0.135 | N | 0.609 | neutral | None | None | None | None | I |
| S/K | 0.6071 | likely_pathogenic | 0.5684 | pathogenic | -0.672 | Destabilizing | 0.004 | N | 0.189 | neutral | None | None | None | None | I |
| S/L | 0.0927 | likely_benign | 0.0846 | benign | -0.196 | Destabilizing | 0.061 | N | 0.493 | neutral | None | None | None | None | I |
| S/M | 0.1875 | likely_benign | 0.1763 | benign | 0.194 | Stabilizing | 0.69 | D | 0.561 | neutral | None | None | None | None | I |
| S/N | 0.1558 | likely_benign | 0.1462 | benign | -0.456 | Destabilizing | None | N | 0.205 | neutral | None | None | None | None | I |
| S/P | 0.4825 | ambiguous | 0.4121 | ambiguous | -0.278 | Destabilizing | 0.113 | N | 0.599 | neutral | N | 0.504143114 | None | None | I |
| S/Q | 0.4479 | ambiguous | 0.4205 | ambiguous | -0.722 | Destabilizing | 0.238 | N | 0.494 | neutral | None | None | None | None | I |
| S/R | 0.4868 | ambiguous | 0.4518 | ambiguous | -0.444 | Destabilizing | 0.135 | N | 0.537 | neutral | None | None | None | None | I |
| S/T | 0.0725 | likely_benign | 0.0717 | benign | -0.504 | Destabilizing | None | N | 0.147 | neutral | N | 0.477435548 | None | None | I |
| S/V | 0.1399 | likely_benign | 0.1306 | benign | -0.278 | Destabilizing | 0.024 | N | 0.49 | neutral | None | None | None | None | I |
| S/W | 0.3225 | likely_benign | 0.2902 | benign | -0.947 | Destabilizing | 0.893 | D | 0.581 | neutral | None | None | None | None | I |
| S/Y | 0.1791 | likely_benign | 0.1521 | benign | -0.687 | Destabilizing | 0.001 | N | 0.428 | neutral | N | 0.507359118 | 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.