Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2561 | 7906;7907;7908 | chr2:178773283;178773282;178773281 | chr2:179638010;179638009;179638008 |
| N2AB | 2561 | 7906;7907;7908 | chr2:178773283;178773282;178773281 | chr2:179638010;179638009;179638008 |
| N2A | 2561 | 7906;7907;7908 | chr2:178773283;178773282;178773281 | chr2:179638010;179638009;179638008 |
| N2B | 2515 | 7768;7769;7770 | chr2:178773283;178773282;178773281 | chr2:179638010;179638009;179638008 |
| Novex-1 | 2515 | 7768;7769;7770 | chr2:178773283;178773282;178773281 | chr2:179638010;179638009;179638008 |
| Novex-2 | 2515 | 7768;7769;7770 | chr2:178773283;178773282;178773281 | chr2:179638010;179638009;179638008 |
| Novex-3 | 2561 | 7906;7907;7908 | chr2:178773283;178773282;178773281 | chr2:179638010;179638009;179638008 |
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 | 0.998 | N | 0.615 | 0.323 | 0.579008800273 | gnomAD-4.0.0 | 1.59086E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8567E-06 | 0 | 0 |
| I/T | rs747031357  |
-1.804 | 0.989 | D | 0.645 | 0.633 | 0.762922086239 | gnomAD-2.1.1 | 2.13E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.3071E-04 | None | 0 | 7.76E-06 | 1.39005E-04 |
| I/T | rs747031357 |
-1.804 | 0.989 | D | 0.645 | 0.633 | 0.762922086239 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 2.07039E-04 | 0 |
| I/T | rs747031357 |
-1.804 | 0.989 | D | 0.645 | 0.633 | 0.762922086239 | gnomAD-4.0.0 | 1.98277E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.18644E-05 | 1.53711E-04 | 6.40205E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.5888 | likely_pathogenic | 0.5727 | pathogenic | -1.413 | Destabilizing | 0.992 | D | 0.503 | neutral | None | None | None | None | N |
| I/C | 0.8703 | likely_pathogenic | 0.8628 | pathogenic | -1.172 | Destabilizing | 1.0 | D | 0.643 | neutral | None | None | None | None | N |
| I/D | 0.9644 | likely_pathogenic | 0.9588 | pathogenic | -0.655 | Destabilizing | 1.0 | D | 0.768 | deleterious | None | None | None | None | N |
| I/E | 0.8985 | likely_pathogenic | 0.884 | pathogenic | -0.61 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | N |
| I/F | 0.4028 | ambiguous | 0.3894 | ambiguous | -0.886 | Destabilizing | 0.998 | D | 0.642 | neutral | N | 0.506628126 | None | None | N |
| I/G | 0.9192 | likely_pathogenic | 0.9093 | pathogenic | -1.724 | Destabilizing | 1.0 | D | 0.754 | deleterious | None | None | None | None | N |
| I/H | 0.9086 | likely_pathogenic | 0.901 | pathogenic | -0.746 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| I/K | 0.8131 | likely_pathogenic | 0.7936 | pathogenic | -0.957 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | N |
| I/L | 0.2671 | likely_benign | 0.2571 | benign | -0.62 | Destabilizing | 0.889 | D | 0.415 | neutral | N | 0.499694492 | None | None | N |
| I/M | 0.1718 | likely_benign | 0.1711 | benign | -0.808 | Destabilizing | 0.998 | D | 0.615 | neutral | N | 0.509503073 | None | None | N |
| I/N | 0.7225 | likely_pathogenic | 0.6904 | pathogenic | -0.968 | Destabilizing | 0.999 | D | 0.761 | deleterious | D | 0.596385455 | None | None | N |
| I/P | 0.9226 | likely_pathogenic | 0.9108 | pathogenic | -0.856 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | N |
| I/Q | 0.853 | likely_pathogenic | 0.8408 | pathogenic | -1.001 | Destabilizing | 1.0 | D | 0.756 | deleterious | None | None | None | None | N |
| I/R | 0.7572 | likely_pathogenic | 0.7321 | pathogenic | -0.523 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| I/S | 0.6706 | likely_pathogenic | 0.6466 | pathogenic | -1.58 | Destabilizing | 0.998 | D | 0.696 | prob.neutral | D | 0.528981829 | None | None | N |
| I/T | 0.3817 | ambiguous | 0.3675 | ambiguous | -1.396 | Destabilizing | 0.989 | D | 0.645 | neutral | D | 0.552509017 | None | None | N |
| I/V | 0.1168 | likely_benign | 0.1155 | benign | -0.856 | Destabilizing | 0.333 | N | 0.209 | neutral | N | 0.477461948 | None | None | N |
| I/W | 0.9449 | likely_pathogenic | 0.9452 | pathogenic | -0.913 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | N |
| I/Y | 0.834 | likely_pathogenic | 0.8205 | pathogenic | -0.703 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | 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.