Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16477 | 49654;49655;49656 | chr2:178613854;178613853;178613852 | chr2:179478581;179478580;179478579 |
| N2AB | 14836 | 44731;44732;44733 | chr2:178613854;178613853;178613852 | chr2:179478581;179478580;179478579 |
| N2A | 13909 | 41950;41951;41952 | chr2:178613854;178613853;178613852 | chr2:179478581;179478580;179478579 |
| N2B | 7412 | 22459;22460;22461 | chr2:178613854;178613853;178613852 | chr2:179478581;179478580;179478579 |
| Novex-1 | 7537 | 22834;22835;22836 | chr2:178613854;178613853;178613852 | chr2:179478581;179478580;179478579 |
| Novex-2 | 7604 | 23035;23036;23037 | chr2:178613854;178613853;178613852 | chr2:179478581;179478580;179478579 |
| 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 | rs762353962  |
-0.585 | 1.0 | D | 0.438 | 0.306 | 0.342168650903 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| D/E | rs762353962 |
-0.585 | 1.0 | D | 0.438 | 0.306 | 0.342168650903 | gnomAD-4.0.0 | 1.59412E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86329E-06 | 0 | 0 |
| D/G | rs765432965 |
-0.681 | 1.0 | D | 0.719 | 0.519 | 0.473616572423 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | I | None | 0 | 2.91E-05 | None | 0 | 0 | None | 3.28E-05 | None | 0 | 0 | 0 |
| D/G | rs765432965 |
-0.681 | 1.0 | D | 0.719 | 0.519 | 0.473616572423 | gnomAD-4.0.0 | 3.18867E-06 | None | None | None | None | I | None | 0 | 2.29011E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02994E-05 |
| D/N | rs1219575984 |
None | 1.0 | N | 0.689 | 0.392 | 0.435699915968 | gnomAD-4.0.0 | 1.5943E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86364E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.9009 | likely_pathogenic | 0.8629 | pathogenic | -0.254 | Destabilizing | 1.0 | D | 0.726 | prob.delet. | D | 0.589793214 | None | None | I |
| D/C | 0.9851 | likely_pathogenic | 0.9775 | pathogenic | 0.124 | Stabilizing | 1.0 | D | 0.638 | neutral | None | None | None | None | I |
| D/E | 0.9261 | likely_pathogenic | 0.8953 | pathogenic | -0.634 | Destabilizing | 1.0 | D | 0.438 | neutral | D | 0.582253375 | None | None | I |
| D/F | 0.9876 | likely_pathogenic | 0.9831 | pathogenic | -0.509 | Destabilizing | 1.0 | D | 0.643 | neutral | None | None | None | None | I |
| D/G | 0.8671 | likely_pathogenic | 0.8283 | pathogenic | -0.508 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | D | 0.610385716 | None | None | I |
| D/H | 0.9402 | likely_pathogenic | 0.9129 | pathogenic | -0.897 | Destabilizing | 1.0 | D | 0.633 | neutral | D | 0.657236631 | None | None | I |
| D/I | 0.9769 | likely_pathogenic | 0.9633 | pathogenic | 0.377 | Stabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | I |
| D/K | 0.9715 | likely_pathogenic | 0.9606 | pathogenic | 0.021 | Stabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | I |
| D/L | 0.9701 | likely_pathogenic | 0.9547 | pathogenic | 0.377 | Stabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | I |
| D/M | 0.989 | likely_pathogenic | 0.9816 | pathogenic | 0.818 | Stabilizing | 1.0 | D | 0.63 | neutral | None | None | None | None | I |
| D/N | 0.286 | likely_benign | 0.2433 | benign | -0.215 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | N | 0.49761147 | None | None | I |
| D/P | 0.9859 | likely_pathogenic | 0.982 | pathogenic | 0.191 | Stabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | I |
| D/Q | 0.976 | likely_pathogenic | 0.9626 | pathogenic | -0.154 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | I |
| D/R | 0.9744 | likely_pathogenic | 0.9642 | pathogenic | -0.085 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | I |
| D/S | 0.6276 | likely_pathogenic | 0.5384 | ambiguous | -0.366 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | I |
| D/T | 0.7394 | likely_pathogenic | 0.6631 | pathogenic | -0.165 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | I |
| D/V | 0.9368 | likely_pathogenic | 0.9078 | pathogenic | 0.191 | Stabilizing | 1.0 | D | 0.705 | prob.neutral | D | 0.617324801 | None | None | I |
| D/W | 0.9977 | likely_pathogenic | 0.997 | pathogenic | -0.527 | Destabilizing | 1.0 | D | 0.641 | neutral | None | None | None | None | I |
| D/Y | 0.9101 | likely_pathogenic | 0.8833 | pathogenic | -0.312 | Destabilizing | 1.0 | D | 0.626 | neutral | D | 0.717697412 | 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.