Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20203 | 60832;60833;60834 | chr2:178591118;178591117;178591116 | chr2:179455845;179455844;179455843 |
| N2AB | 18562 | 55909;55910;55911 | chr2:178591118;178591117;178591116 | chr2:179455845;179455844;179455843 |
| N2A | 17635 | 53128;53129;53130 | chr2:178591118;178591117;178591116 | chr2:179455845;179455844;179455843 |
| N2B | 11138 | 33637;33638;33639 | chr2:178591118;178591117;178591116 | chr2:179455845;179455844;179455843 |
| Novex-1 | 11263 | 34012;34013;34014 | chr2:178591118;178591117;178591116 | chr2:179455845;179455844;179455843 |
| Novex-2 | 11330 | 34213;34214;34215 | chr2:178591118;178591117;178591116 | chr2:179455845;179455844;179455843 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | None | None | 0.011 | D | 0.263 | 0.269 | 0.221019684889 | gnomAD-4.0.0 | 6.84432E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99675E-07 | 0 | 0 |
| P/L | rs753978233  |
-0.111 | 0.026 | N | 0.463 | 0.401 | 0.468420198123 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| P/L | rs753978233 |
-0.111 | 0.026 | N | 0.463 | 0.401 | 0.468420198123 | gnomAD-4.0.0 | 1.59246E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8603E-06 | 0 | 0 |
| P/S | rs757129250 |
-0.231 | 0.811 | N | 0.553 | 0.307 | 0.312608672186 | gnomAD-2.1.1 | 1.79E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.13E-05 | 1.40845E-04 |
| P/S | rs757129250 |
-0.231 | 0.811 | N | 0.553 | 0.307 | 0.312608672186 | 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 |
| P/S | rs757129250 |
-0.231 | 0.811 | N | 0.553 | 0.307 | 0.312608672186 | gnomAD-4.0.0 | 6.19974E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.63053E-06 | 0 | 1.60138E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0903 | likely_benign | 0.0948 | benign | -0.637 | Destabilizing | 0.011 | N | 0.263 | neutral | D | 0.526525069 | None | None | I |
| P/C | 0.6173 | likely_pathogenic | 0.6597 | pathogenic | -0.642 | Destabilizing | 0.999 | D | 0.698 | prob.neutral | None | None | None | None | I |
| P/D | 0.4844 | ambiguous | 0.5228 | ambiguous | -0.363 | Destabilizing | 0.988 | D | 0.599 | neutral | None | None | None | None | I |
| P/E | 0.3127 | likely_benign | 0.3379 | benign | -0.475 | Destabilizing | 0.976 | D | 0.528 | neutral | None | None | None | None | I |
| P/F | 0.6649 | likely_pathogenic | 0.6888 | pathogenic | -0.824 | Destabilizing | 0.976 | D | 0.713 | prob.delet. | None | None | None | None | I |
| P/G | 0.4118 | ambiguous | 0.4523 | ambiguous | -0.791 | Destabilizing | 0.851 | D | 0.581 | neutral | None | None | None | None | I |
| P/H | 0.2716 | likely_benign | 0.301 | benign | -0.347 | Destabilizing | 0.999 | D | 0.685 | prob.neutral | N | 0.513608137 | None | None | I |
| P/I | 0.4137 | ambiguous | 0.4247 | ambiguous | -0.377 | Destabilizing | 0.952 | D | 0.631 | neutral | None | None | None | None | I |
| P/K | 0.3484 | ambiguous | 0.3916 | ambiguous | -0.499 | Destabilizing | 0.976 | D | 0.528 | neutral | None | None | None | None | I |
| P/L | 0.163 | likely_benign | 0.173 | benign | -0.377 | Destabilizing | 0.026 | N | 0.463 | neutral | N | 0.50581023 | None | None | I |
| P/M | 0.3391 | likely_benign | 0.3453 | ambiguous | -0.303 | Destabilizing | 0.993 | D | 0.682 | prob.neutral | None | None | None | None | I |
| P/N | 0.3737 | ambiguous | 0.4002 | ambiguous | -0.216 | Destabilizing | 0.988 | D | 0.696 | prob.neutral | None | None | None | None | I |
| P/Q | 0.1904 | likely_benign | 0.2086 | benign | -0.483 | Destabilizing | 0.988 | D | 0.6 | neutral | None | None | None | None | I |
| P/R | 0.2694 | likely_benign | 0.3027 | benign | 0.052 | Stabilizing | 0.984 | D | 0.7 | prob.neutral | N | 0.490730942 | None | None | I |
| P/S | 0.1591 | likely_benign | 0.1715 | benign | -0.616 | Destabilizing | 0.811 | D | 0.553 | neutral | N | 0.473169665 | None | None | I |
| P/T | 0.1322 | likely_benign | 0.1408 | benign | -0.624 | Destabilizing | 0.896 | D | 0.53 | neutral | N | 0.48840031 | None | None | I |
| P/V | 0.2515 | likely_benign | 0.2581 | benign | -0.428 | Destabilizing | 0.851 | D | 0.589 | neutral | None | None | None | None | I |
| P/W | 0.7859 | likely_pathogenic | 0.8156 | pathogenic | -0.885 | Destabilizing | 0.999 | D | 0.742 | deleterious | None | None | None | None | I |
| P/Y | 0.6095 | likely_pathogenic | 0.6376 | pathogenic | -0.59 | Destabilizing | 0.988 | D | 0.712 | prob.delet. | 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.