Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13745 | 41458;41459;41460 | chr2:178636494;178636493;178636492 | chr2:179501221;179501220;179501219 |
| N2AB | 12104 | 36535;36536;36537 | chr2:178636494;178636493;178636492 | chr2:179501221;179501220;179501219 |
| N2A | 11177 | 33754;33755;33756 | chr2:178636494;178636493;178636492 | chr2:179501221;179501220;179501219 |
| N2B | 4680 | 14263;14264;14265 | chr2:178636494;178636493;178636492 | chr2:179501221;179501220;179501219 |
| Novex-1 | 4805 | 14638;14639;14640 | chr2:178636494;178636493;178636492 | chr2:179501221;179501220;179501219 |
| Novex-2 | 4872 | 14839;14840;14841 | chr2:178636494;178636493;178636492 | chr2:179501221;179501220;179501219 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | None | None | 1.0 | D | 0.748 | 0.573 | 0.666729369348 | gnomAD-4.0.0 | 6.84346E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15947E-05 | 0 |
| I/V | rs770466417  |
-1.607 | 0.993 | D | 0.392 | 0.479 | 0.801257991606 | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.63452E-04 | None | 0 | 0 | 0 |
| I/V | rs770466417 |
-1.607 | 0.993 | D | 0.392 | 0.479 | 0.801257991606 | gnomAD-4.0.0 | 1.02651E-05 | None | None | None | None | N | None | 2.98882E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99598E-07 | 1.50732E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9948 | likely_pathogenic | 0.9966 | pathogenic | -3.118 | Highly Destabilizing | 0.999 | D | 0.707 | prob.neutral | None | None | None | None | N |
| I/C | 0.9942 | likely_pathogenic | 0.9952 | pathogenic | -2.442 | Highly Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| I/D | 0.9997 | likely_pathogenic | 0.9998 | pathogenic | -3.76 | Highly Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| I/E | 0.9993 | likely_pathogenic | 0.9995 | pathogenic | -3.459 | Highly Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| I/F | 0.8729 | likely_pathogenic | 0.9236 | pathogenic | -1.772 | Destabilizing | 1.0 | D | 0.8 | deleterious | D | 0.650545128 | None | None | N |
| I/G | 0.9993 | likely_pathogenic | 0.9996 | pathogenic | -3.691 | Highly Destabilizing | 1.0 | D | 0.846 | deleterious | None | None | None | None | N |
| I/H | 0.9981 | likely_pathogenic | 0.9989 | pathogenic | -3.229 | Highly Destabilizing | 1.0 | D | 0.854 | deleterious | None | None | None | None | N |
| I/K | 0.9978 | likely_pathogenic | 0.9986 | pathogenic | -2.436 | Highly Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| I/L | 0.491 | ambiguous | 0.5377 | ambiguous | -1.378 | Destabilizing | 0.993 | D | 0.409 | neutral | D | 0.573324255 | None | None | N |
| I/M | 0.6339 | likely_pathogenic | 0.6887 | pathogenic | -1.59 | Destabilizing | 1.0 | D | 0.748 | deleterious | D | 0.711554708 | None | None | N |
| I/N | 0.9954 | likely_pathogenic | 0.9971 | pathogenic | -3.091 | Highly Destabilizing | 1.0 | D | 0.864 | deleterious | D | 0.793502728 | None | None | N |
| I/P | 0.9996 | likely_pathogenic | 0.9997 | pathogenic | -1.953 | Destabilizing | 1.0 | D | 0.863 | deleterious | None | None | None | None | N |
| I/Q | 0.9983 | likely_pathogenic | 0.999 | pathogenic | -2.782 | Highly Destabilizing | 1.0 | D | 0.875 | deleterious | None | None | None | None | N |
| I/R | 0.9962 | likely_pathogenic | 0.9976 | pathogenic | -2.326 | Highly Destabilizing | 1.0 | D | 0.863 | deleterious | None | None | None | None | N |
| I/S | 0.9957 | likely_pathogenic | 0.9973 | pathogenic | -3.653 | Highly Destabilizing | 1.0 | D | 0.837 | deleterious | D | 0.793502728 | None | None | N |
| I/T | 0.9938 | likely_pathogenic | 0.9957 | pathogenic | -3.207 | Highly Destabilizing | 1.0 | D | 0.8 | deleterious | D | 0.793712584 | None | None | N |
| I/V | 0.2797 | likely_benign | 0.264 | benign | -1.953 | Destabilizing | 0.993 | D | 0.392 | neutral | D | 0.547782821 | None | None | N |
| I/W | 0.9983 | likely_pathogenic | 0.999 | pathogenic | -2.205 | Highly Destabilizing | 1.0 | D | 0.852 | deleterious | None | None | None | None | N |
| I/Y | 0.9918 | likely_pathogenic | 0.9953 | pathogenic | -2.093 | Highly Destabilizing | 1.0 | D | 0.818 | deleterious | 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.