Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24765 | 74518;74519;74520 | chr2:178571839;178571838;178571837 | chr2:179436566;179436565;179436564 |
| N2AB | 23124 | 69595;69596;69597 | chr2:178571839;178571838;178571837 | chr2:179436566;179436565;179436564 |
| N2A | 22197 | 66814;66815;66816 | chr2:178571839;178571838;178571837 | chr2:179436566;179436565;179436564 |
| N2B | 15700 | 47323;47324;47325 | chr2:178571839;178571838;178571837 | chr2:179436566;179436565;179436564 |
| Novex-1 | 15825 | 47698;47699;47700 | chr2:178571839;178571838;178571837 | chr2:179436566;179436565;179436564 |
| Novex-2 | 15892 | 47899;47900;47901 | chr2:178571839;178571838;178571837 | chr2:179436566;179436565;179436564 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/D | rs756519457  |
-0.154 | 0.067 | N | 0.216 | 0.051 | 0.228597637076 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 0 | 0 |
| E/D | rs756519457 |
-0.154 | 0.067 | N | 0.216 | 0.051 | 0.228597637076 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 9.42E-05 | 0 | 0 | 0 | 0 |
| E/D | rs756519457 |
-0.154 | 0.067 | N | 0.216 | 0.051 | 0.228597637076 | gnomAD-4.0.0 | 3.84453E-06 | None | None | None | None | N | None | 0 | 3.39018E-05 | None | 0 | 0 | None | 1.56902E-05 | 0 | 0 | 0 | 0 |
| E/G | rs963867892 |
None | 0.988 | D | 0.685 | 0.38 | 0.59199265086 | gnomAD-4.0.0 | 6.00161E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.56251E-06 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.128 | likely_benign | 0.1217 | benign | -0.312 | Destabilizing | 0.958 | D | 0.631 | neutral | D | 0.534270265 | None | None | N |
| E/C | 0.7183 | likely_pathogenic | 0.6993 | pathogenic | 0.295 | Stabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | N |
| E/D | 0.1142 | likely_benign | 0.1206 | benign | -0.2 | Destabilizing | 0.067 | N | 0.216 | neutral | N | 0.477435548 | None | None | N |
| E/F | 0.5301 | ambiguous | 0.5193 | ambiguous | -0.419 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | N |
| E/G | 0.169 | likely_benign | 0.1672 | benign | -0.493 | Destabilizing | 0.988 | D | 0.685 | prob.neutral | D | 0.528480444 | None | None | N |
| E/H | 0.3091 | likely_benign | 0.2976 | benign | -0.416 | Destabilizing | 1.0 | D | 0.628 | neutral | None | None | None | None | N |
| E/I | 0.1802 | likely_benign | 0.1703 | benign | 0.12 | Stabilizing | 0.995 | D | 0.766 | deleterious | None | None | None | None | N |
| E/K | 0.1207 | likely_benign | 0.1108 | benign | 0.537 | Stabilizing | 0.958 | D | 0.538 | neutral | N | 0.508275743 | None | None | N |
| E/L | 0.2683 | likely_benign | 0.2566 | benign | 0.12 | Stabilizing | 0.995 | D | 0.764 | deleterious | None | None | None | None | N |
| E/M | 0.3091 | likely_benign | 0.2918 | benign | 0.398 | Stabilizing | 1.0 | D | 0.7 | prob.neutral | None | None | None | None | N |
| E/N | 0.1814 | likely_benign | 0.1808 | benign | 0.329 | Stabilizing | 0.982 | D | 0.66 | neutral | None | None | None | None | N |
| E/P | 0.8454 | likely_pathogenic | 0.8613 | pathogenic | -0.004 | Destabilizing | 0.995 | D | 0.749 | deleterious | None | None | None | None | N |
| E/Q | 0.116 | likely_benign | 0.1086 | benign | 0.345 | Stabilizing | 0.994 | D | 0.588 | neutral | N | 0.521783758 | None | None | N |
| E/R | 0.2153 | likely_benign | 0.2031 | benign | 0.521 | Stabilizing | 0.995 | D | 0.688 | prob.neutral | None | None | None | None | N |
| E/S | 0.1429 | likely_benign | 0.1386 | benign | 0.167 | Stabilizing | 0.968 | D | 0.576 | neutral | None | None | None | None | N |
| E/T | 0.1395 | likely_benign | 0.1313 | benign | 0.316 | Stabilizing | 0.991 | D | 0.713 | prob.delet. | None | None | None | None | N |
| E/V | 0.1214 | likely_benign | 0.1138 | benign | -0.004 | Destabilizing | 0.994 | D | 0.749 | deleterious | D | 0.524015986 | None | None | N |
| E/W | 0.8169 | likely_pathogenic | 0.8131 | pathogenic | -0.341 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | N |
| E/Y | 0.4553 | ambiguous | 0.4536 | ambiguous | -0.184 | Destabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | 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.