Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24953 | 75082;75083;75084 | chr2:178571275;178571274;178571273 | chr2:179436002;179436001;179436000 |
| N2AB | 23312 | 70159;70160;70161 | chr2:178571275;178571274;178571273 | chr2:179436002;179436001;179436000 |
| N2A | 22385 | 67378;67379;67380 | chr2:178571275;178571274;178571273 | chr2:179436002;179436001;179436000 |
| N2B | 15888 | 47887;47888;47889 | chr2:178571275;178571274;178571273 | chr2:179436002;179436001;179436000 |
| Novex-1 | 16013 | 48262;48263;48264 | chr2:178571275;178571274;178571273 | chr2:179436002;179436001;179436000 |
| Novex-2 | 16080 | 48463;48464;48465 | chr2:178571275;178571274;178571273 | chr2:179436002;179436001;179436000 |
| 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/N | rs370142941  |
-0.146 | 0.942 | N | 0.572 | 0.408 | 0.676505548274 | gnomAD-4.0.0 | 1.36862E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.31879E-05 | 0 |
| I/T | rs370142941 |
-0.454 | 0.822 | N | 0.521 | 0.219 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs1420626943 |
-0.202 | 0.489 | N | 0.476 | 0.075 | 0.451118754121 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.58E-05 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs1420626943 |
-0.202 | 0.489 | N | 0.476 | 0.075 | 0.451118754121 | gnomAD-4.0.0 | 1.5918E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.77577E-05 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.8822 | likely_pathogenic | 0.8677 | pathogenic | -0.521 | Destabilizing | 0.754 | D | 0.519 | neutral | None | None | None | None | I |
| I/C | 0.9607 | likely_pathogenic | 0.956 | pathogenic | -0.887 | Destabilizing | 0.998 | D | 0.615 | neutral | None | None | None | None | I |
| I/D | 0.9813 | likely_pathogenic | 0.9774 | pathogenic | -0.156 | Destabilizing | 0.956 | D | 0.577 | neutral | None | None | None | None | I |
| I/E | 0.9812 | likely_pathogenic | 0.9779 | pathogenic | -0.235 | Destabilizing | 0.915 | D | 0.521 | neutral | None | None | None | None | I |
| I/F | 0.5428 | ambiguous | 0.5314 | ambiguous | -0.628 | Destabilizing | 0.942 | D | 0.553 | neutral | N | 0.485674378 | None | None | I |
| I/G | 0.9718 | likely_pathogenic | 0.9669 | pathogenic | -0.62 | Destabilizing | 0.956 | D | 0.546 | neutral | None | None | None | None | I |
| I/H | 0.943 | likely_pathogenic | 0.9403 | pathogenic | 0.09 | Stabilizing | 0.994 | D | 0.593 | neutral | None | None | None | None | I |
| I/K | 0.9384 | likely_pathogenic | 0.9383 | pathogenic | -0.378 | Destabilizing | 0.019 | N | 0.514 | neutral | None | None | None | None | I |
| I/L | 0.1718 | likely_benign | 0.1852 | benign | -0.372 | Destabilizing | 0.006 | N | 0.257 | neutral | N | 0.438556581 | None | None | I |
| I/M | 0.3243 | likely_benign | 0.3153 | benign | -0.692 | Destabilizing | 0.942 | D | 0.561 | neutral | N | 0.514054417 | None | None | I |
| I/N | 0.8654 | likely_pathogenic | 0.8531 | pathogenic | -0.293 | Destabilizing | 0.942 | D | 0.572 | neutral | N | 0.47120493 | None | None | I |
| I/P | 0.913 | likely_pathogenic | 0.9175 | pathogenic | -0.396 | Destabilizing | 0.978 | D | 0.573 | neutral | None | None | None | None | I |
| I/Q | 0.9526 | likely_pathogenic | 0.9476 | pathogenic | -0.437 | Destabilizing | 0.956 | D | 0.579 | neutral | None | None | None | None | I |
| I/R | 0.8914 | likely_pathogenic | 0.8931 | pathogenic | 0.068 | Stabilizing | 0.915 | D | 0.563 | neutral | None | None | None | None | I |
| I/S | 0.8596 | likely_pathogenic | 0.8479 | pathogenic | -0.703 | Destabilizing | 0.822 | D | 0.472 | neutral | N | 0.444866477 | None | None | I |
| I/T | 0.9033 | likely_pathogenic | 0.8872 | pathogenic | -0.682 | Destabilizing | 0.822 | D | 0.521 | neutral | N | 0.489580047 | None | None | I |
| I/V | 0.1996 | likely_benign | 0.2004 | benign | -0.396 | Destabilizing | 0.489 | N | 0.476 | neutral | N | 0.467647337 | None | None | I |
| I/W | 0.9605 | likely_pathogenic | 0.9579 | pathogenic | -0.635 | Destabilizing | 0.998 | D | 0.635 | neutral | None | None | None | None | I |
| I/Y | 0.8608 | likely_pathogenic | 0.8597 | pathogenic | -0.422 | Destabilizing | 0.993 | D | 0.565 | neutral | None | None | 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.