Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13900 | 41923;41924;41925 | chr2:178635626;178635625;178635624 | chr2:179500353;179500352;179500351 |
| N2AB | 12259 | 37000;37001;37002 | chr2:178635626;178635625;178635624 | chr2:179500353;179500352;179500351 |
| N2A | 11332 | 34219;34220;34221 | chr2:178635626;178635625;178635624 | chr2:179500353;179500352;179500351 |
| N2B | 4835 | 14728;14729;14730 | chr2:178635626;178635625;178635624 | chr2:179500353;179500352;179500351 |
| Novex-1 | 4960 | 15103;15104;15105 | chr2:178635626;178635625;178635624 | chr2:179500353;179500352;179500351 |
| Novex-2 | 5027 | 15304;15305;15306 | chr2:178635626;178635625;178635624 | chr2:179500353;179500352;179500351 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/H | rs1188616797  |
-0.277 | 0.862 | N | 0.367 | 0.403 | 0.260249123532 | gnomAD-2.1.1 | 9.13E-06 | None | None | None | None | N | None | 7.44E-05 | 0 | None | 0 | 0 | None | 3.66E-05 | None | 0 | 0 | 0 |
| D/H | rs1188616797 |
-0.277 | 0.862 | N | 0.367 | 0.403 | 0.260249123532 | gnomAD-4.0.0 | 3.28008E-06 | None | None | None | None | N | None | 5.72541E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.49107E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.5521 | ambiguous | 0.4738 | ambiguous | -0.188 | Destabilizing | 0.104 | N | 0.428 | neutral | N | 0.461243714 | None | None | N |
| D/C | 0.9584 | likely_pathogenic | 0.939 | pathogenic | -0.018 | Destabilizing | 0.962 | D | 0.657 | prob.neutral | None | None | None | None | N |
| D/E | 0.2793 | likely_benign | 0.2883 | benign | -0.221 | Destabilizing | 0.001 | N | 0.283 | neutral | N | 0.443014917 | None | None | N |
| D/F | 0.9116 | likely_pathogenic | 0.8877 | pathogenic | -0.125 | Destabilizing | 0.962 | D | 0.647 | neutral | None | None | None | None | N |
| D/G | 0.5116 | ambiguous | 0.4416 | ambiguous | -0.383 | Destabilizing | 0.001 | N | 0.309 | neutral | N | 0.443902459 | None | None | N |
| D/H | 0.8379 | likely_pathogenic | 0.7767 | pathogenic | 0.066 | Stabilizing | 0.862 | D | 0.367 | neutral | N | 0.504124514 | None | None | N |
| D/I | 0.8417 | likely_pathogenic | 0.7898 | pathogenic | 0.276 | Stabilizing | 0.687 | D | 0.705 | prob.delet. | None | None | None | None | N |
| D/K | 0.8943 | likely_pathogenic | 0.8414 | pathogenic | 0.241 | Stabilizing | 0.134 | N | 0.349 | neutral | None | None | None | None | N |
| D/L | 0.8221 | likely_pathogenic | 0.7799 | pathogenic | 0.276 | Stabilizing | 0.519 | D | 0.719 | prob.delet. | None | None | None | None | N |
| D/M | 0.9197 | likely_pathogenic | 0.9023 | pathogenic | 0.308 | Stabilizing | 0.962 | D | 0.701 | prob.delet. | None | None | None | None | N |
| D/N | 0.2778 | likely_benign | 0.2239 | benign | 0.009 | Stabilizing | 0.189 | N | 0.408 | neutral | N | 0.448080819 | None | None | N |
| D/P | 0.8941 | likely_pathogenic | 0.8235 | pathogenic | 0.144 | Stabilizing | 0.687 | D | 0.401 | neutral | None | None | None | None | N |
| D/Q | 0.8216 | likely_pathogenic | 0.7719 | pathogenic | 0.05 | Stabilizing | 0.351 | N | 0.389 | neutral | None | None | None | None | N |
| D/R | 0.9291 | likely_pathogenic | 0.8961 | pathogenic | 0.436 | Stabilizing | 0.351 | N | 0.615 | neutral | None | None | None | None | N |
| D/S | 0.4494 | ambiguous | 0.3829 | ambiguous | -0.12 | Destabilizing | 0.134 | N | 0.357 | neutral | None | None | None | None | N |
| D/T | 0.6649 | likely_pathogenic | 0.6114 | pathogenic | 0.029 | Stabilizing | 0.519 | D | 0.363 | neutral | None | None | None | None | N |
| D/V | 0.662 | likely_pathogenic | 0.5858 | pathogenic | 0.144 | Stabilizing | 0.449 | N | 0.71 | prob.delet. | N | 0.500478255 | None | None | N |
| D/W | 0.9884 | likely_pathogenic | 0.9832 | pathogenic | -0.021 | Destabilizing | 0.962 | D | 0.647 | neutral | None | None | None | None | N |
| D/Y | 0.6405 | likely_pathogenic | 0.5857 | pathogenic | 0.1 | Stabilizing | 0.95 | D | 0.645 | neutral | N | 0.504124514 | 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.