Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19100 | 57523;57524;57525 | chr2:178597784;178597783;178597782 | chr2:179462511;179462510;179462509 |
| N2AB | 17459 | 52600;52601;52602 | chr2:178597784;178597783;178597782 | chr2:179462511;179462510;179462509 |
| N2A | 16532 | 49819;49820;49821 | chr2:178597784;178597783;178597782 | chr2:179462511;179462510;179462509 |
| N2B | 10035 | 30328;30329;30330 | chr2:178597784;178597783;178597782 | chr2:179462511;179462510;179462509 |
| Novex-1 | 10160 | 30703;30704;30705 | chr2:178597784;178597783;178597782 | chr2:179462511;179462510;179462509 |
| Novex-2 | 10227 | 30904;30905;30906 | chr2:178597784;178597783;178597782 | chr2:179462511;179462510;179462509 |
| 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/E | rs876658069  |
-0.173 | 0.02 | N | 0.269 | 0.079 | 0.101711395817 | gnomAD-2.1.1 | 7.16E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.03681E-04 | None | 0 | None | 0 | 0 | 0 |
| D/E | rs876658069 |
-0.173 | 0.02 | N | 0.269 | 0.079 | 0.101711395817 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.94099E-04 | None | 0 | 0 | 0 | 0 | 0 |
| D/E | rs876658069 |
-0.173 | 0.02 | N | 0.269 | 0.079 | 0.101711395817 | gnomAD-4.0.0 | 1.73574E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 4.47808E-05 | None | 0 | 1.6469E-04 | 2.03464E-05 | 0 | 1.60164E-05 |
| D/N | rs2154189970 |
None | 0.939 | N | 0.365 | 0.34 | 0.431931272081 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs2154189970 |
None | 0.939 | N | 0.365 | 0.34 | 0.431931272081 | gnomAD-4.0.0 | 5.47564E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.49816E-06 | 0 | 4.97166E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.669 | likely_pathogenic | 0.752 | pathogenic | -0.08 | Destabilizing | 0.939 | D | 0.428 | neutral | N | 0.521090324 | None | None | N |
| D/C | 0.9557 | likely_pathogenic | 0.972 | pathogenic | -0.13 | Destabilizing | 0.999 | D | 0.628 | neutral | None | None | None | None | N |
| D/E | 0.2633 | likely_benign | 0.2627 | benign | -0.218 | Destabilizing | 0.02 | N | 0.269 | neutral | N | 0.428814882 | None | None | N |
| D/F | 0.9576 | likely_pathogenic | 0.9758 | pathogenic | 0.216 | Stabilizing | 0.998 | D | 0.614 | neutral | None | None | None | None | N |
| D/G | 0.4834 | ambiguous | 0.597 | pathogenic | -0.305 | Destabilizing | 0.969 | D | 0.422 | neutral | N | 0.496492884 | None | None | N |
| D/H | 0.7792 | likely_pathogenic | 0.8502 | pathogenic | 0.504 | Stabilizing | 0.998 | D | 0.449 | neutral | N | 0.496492884 | None | None | N |
| D/I | 0.932 | likely_pathogenic | 0.9541 | pathogenic | 0.47 | Stabilizing | 0.993 | D | 0.631 | neutral | None | None | None | None | N |
| D/K | 0.8428 | likely_pathogenic | 0.8818 | pathogenic | 0.401 | Stabilizing | 0.91 | D | 0.401 | neutral | None | None | None | None | N |
| D/L | 0.8912 | likely_pathogenic | 0.9188 | pathogenic | 0.47 | Stabilizing | 0.986 | D | 0.611 | neutral | None | None | None | None | N |
| D/M | 0.951 | likely_pathogenic | 0.9664 | pathogenic | 0.356 | Stabilizing | 0.999 | D | 0.611 | neutral | None | None | None | None | N |
| D/N | 0.2949 | likely_benign | 0.3514 | ambiguous | -0.132 | Destabilizing | 0.939 | D | 0.365 | neutral | N | 0.477896908 | None | None | N |
| D/P | 0.9239 | likely_pathogenic | 0.9498 | pathogenic | 0.31 | Stabilizing | 0.993 | D | 0.444 | neutral | None | None | None | None | N |
| D/Q | 0.7408 | likely_pathogenic | 0.7847 | pathogenic | -0.04 | Destabilizing | 0.973 | D | 0.332 | neutral | None | None | None | None | N |
| D/R | 0.8754 | likely_pathogenic | 0.917 | pathogenic | 0.66 | Stabilizing | 0.986 | D | 0.539 | neutral | None | None | None | None | N |
| D/S | 0.422 | ambiguous | 0.5221 | ambiguous | -0.205 | Destabilizing | 0.953 | D | 0.361 | neutral | None | None | None | None | N |
| D/T | 0.7321 | likely_pathogenic | 0.7902 | pathogenic | -0.013 | Destabilizing | 0.986 | D | 0.381 | neutral | None | None | None | None | N |
| D/V | 0.8236 | likely_pathogenic | 0.874 | pathogenic | 0.31 | Stabilizing | 0.991 | D | 0.597 | neutral | N | 0.496239395 | None | None | N |
| D/W | 0.981 | likely_pathogenic | 0.9894 | pathogenic | 0.374 | Stabilizing | 0.999 | D | 0.627 | neutral | None | None | None | None | N |
| D/Y | 0.7423 | likely_pathogenic | 0.8295 | pathogenic | 0.467 | Stabilizing | 0.997 | D | 0.616 | neutral | N | 0.496999863 | 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.