Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20240 | 60943;60944;60945 | chr2:178591007;178591006;178591005 | chr2:179455734;179455733;179455732 |
| N2AB | 18599 | 56020;56021;56022 | chr2:178591007;178591006;178591005 | chr2:179455734;179455733;179455732 |
| N2A | 17672 | 53239;53240;53241 | chr2:178591007;178591006;178591005 | chr2:179455734;179455733;179455732 |
| N2B | 11175 | 33748;33749;33750 | chr2:178591007;178591006;178591005 | chr2:179455734;179455733;179455732 |
| Novex-1 | 11300 | 34123;34124;34125 | chr2:178591007;178591006;178591005 | chr2:179455734;179455733;179455732 |
| Novex-2 | 11367 | 34324;34325;34326 | chr2:178591007;178591006;178591005 | chr2:179455734;179455733;179455732 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/R | None | None | 0.017 | N | 0.443 | 0.094 | 0.524166996187 | gnomAD-4.0.0 | 4.80129E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.25001E-06 | 0 | 0 |
| C/Y | rs1054918425  |
-1.378 | None | N | 0.215 | 0.066 | 0.177238962908 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.96E-06 | 0 |
| C/Y | rs1054918425 |
-1.378 | None | N | 0.215 | 0.066 | 0.177238962908 | gnomAD-4.0.0 | 5.47467E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52067E-05 | None | 0 | 0 | 5.39772E-06 | 1.1595E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.3245 | likely_benign | 0.254 | benign | -1.781 | Destabilizing | None | N | 0.057 | neutral | None | None | None | None | N |
| C/D | 0.5487 | ambiguous | 0.4298 | ambiguous | -0.595 | Destabilizing | 0.009 | N | 0.323 | neutral | None | None | None | None | N |
| C/E | 0.5986 | likely_pathogenic | 0.4801 | ambiguous | -0.477 | Destabilizing | 0.009 | N | 0.321 | neutral | None | None | None | None | N |
| C/F | 0.1639 | likely_benign | 0.1109 | benign | -1.131 | Destabilizing | 0.017 | N | 0.411 | neutral | N | 0.471399718 | None | None | N |
| C/G | 0.194 | likely_benign | 0.1631 | benign | -2.098 | Highly Destabilizing | 0.007 | N | 0.312 | neutral | N | 0.420586895 | None | None | N |
| C/H | 0.2617 | likely_benign | 0.1712 | benign | -2.118 | Highly Destabilizing | 0.138 | N | 0.453 | neutral | None | None | None | None | N |
| C/I | 0.3783 | ambiguous | 0.2907 | benign | -0.961 | Destabilizing | 0.009 | N | 0.333 | neutral | None | None | None | None | N |
| C/K | 0.4846 | ambiguous | 0.3517 | ambiguous | -1.072 | Destabilizing | 0.009 | N | 0.341 | neutral | None | None | None | None | N |
| C/L | 0.3377 | likely_benign | 0.2733 | benign | -0.961 | Destabilizing | 0.004 | N | 0.255 | neutral | None | None | None | None | N |
| C/M | 0.4361 | ambiguous | 0.3615 | ambiguous | -0.036 | Destabilizing | 0.245 | N | 0.34 | neutral | None | None | None | None | N |
| C/N | 0.3055 | likely_benign | 0.2301 | benign | -1.122 | Destabilizing | None | N | 0.191 | neutral | None | None | None | None | N |
| C/P | 0.9684 | likely_pathogenic | 0.9543 | pathogenic | -1.209 | Destabilizing | 0.044 | N | 0.469 | neutral | None | None | None | None | N |
| C/Q | 0.3368 | likely_benign | 0.2372 | benign | -1.005 | Destabilizing | 0.001 | N | 0.249 | neutral | None | None | None | None | N |
| C/R | 0.2163 | likely_benign | 0.1485 | benign | -0.971 | Destabilizing | 0.017 | N | 0.443 | neutral | N | 0.355303266 | None | None | N |
| C/S | 0.2016 | likely_benign | 0.1594 | benign | -1.65 | Destabilizing | None | N | 0.113 | neutral | N | 0.385818174 | None | None | N |
| C/T | 0.3204 | likely_benign | 0.2519 | benign | -1.348 | Destabilizing | None | N | 0.112 | neutral | None | None | None | None | N |
| C/V | 0.3217 | likely_benign | 0.2522 | benign | -1.209 | Destabilizing | None | N | 0.107 | neutral | None | None | None | None | N |
| C/W | 0.333 | likely_benign | 0.2441 | benign | -1.163 | Destabilizing | 0.48 | N | 0.401 | neutral | N | 0.446792062 | None | None | N |
| C/Y | 0.1909 | likely_benign | 0.1308 | benign | -1.133 | Destabilizing | None | N | 0.215 | neutral | N | 0.489985479 | 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.