Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27538 | 82837;82838;82839 | chr2:178563520;178563519;178563518 | chr2:179428247;179428246;179428245 |
| N2AB | 25897 | 77914;77915;77916 | chr2:178563520;178563519;178563518 | chr2:179428247;179428246;179428245 |
| N2A | 24970 | 75133;75134;75135 | chr2:178563520;178563519;178563518 | chr2:179428247;179428246;179428245 |
| N2B | 18473 | 55642;55643;55644 | chr2:178563520;178563519;178563518 | chr2:179428247;179428246;179428245 |
| Novex-1 | 18598 | 56017;56018;56019 | chr2:178563520;178563519;178563518 | chr2:179428247;179428246;179428245 |
| Novex-2 | 18665 | 56218;56219;56220 | chr2:178563520;178563519;178563518 | chr2:179428247;179428246;179428245 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/L | rs878933739  |
0.748 | 0.97 | N | 0.498 | 0.395 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| H/L | rs878933739 |
0.748 | 0.97 | N | 0.498 | 0.395 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| H/L | rs878933739 |
0.748 | 0.97 | N | 0.498 | 0.395 | None | gnomAD-4.0.0 | 1.97169E-05 | None | None | None | None | N | None | 7.23659E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| H/R | rs878933739 |
None | 0.942 | N | 0.421 | 0.38 | 0.36076525451 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| H/R | rs878933739 |
None | 0.942 | N | 0.421 | 0.38 | 0.36076525451 | gnomAD-4.0.0 | 2.02991E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.40991E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/A | 0.7701 | likely_pathogenic | 0.7153 | pathogenic | -0.404 | Destabilizing | 0.86 | D | 0.44 | neutral | None | None | None | None | N |
| H/C | 0.2748 | likely_benign | 0.2431 | benign | 0.517 | Stabilizing | 0.998 | D | 0.607 | neutral | None | None | None | None | N |
| H/D | 0.7606 | likely_pathogenic | 0.7246 | pathogenic | -0.157 | Destabilizing | 0.698 | D | 0.431 | neutral | N | 0.518633517 | None | None | N |
| H/E | 0.8176 | likely_pathogenic | 0.7723 | pathogenic | -0.082 | Destabilizing | 0.86 | D | 0.402 | neutral | None | None | None | None | N |
| H/F | 0.6408 | likely_pathogenic | 0.5753 | pathogenic | 0.539 | Stabilizing | 0.993 | D | 0.433 | neutral | None | None | None | None | N |
| H/G | 0.7101 | likely_pathogenic | 0.6811 | pathogenic | -0.753 | Destabilizing | 0.754 | D | 0.415 | neutral | None | None | None | None | N |
| H/I | 0.7817 | likely_pathogenic | 0.7061 | pathogenic | 0.543 | Stabilizing | 0.978 | D | 0.571 | neutral | None | None | None | None | N |
| H/K | 0.5197 | ambiguous | 0.4751 | ambiguous | -0.15 | Destabilizing | 0.86 | D | 0.439 | neutral | None | None | None | None | N |
| H/L | 0.406 | ambiguous | 0.3633 | ambiguous | 0.543 | Stabilizing | 0.97 | D | 0.498 | neutral | N | 0.506512369 | None | None | N |
| H/M | 0.8435 | likely_pathogenic | 0.7924 | pathogenic | 0.461 | Stabilizing | 0.998 | D | 0.512 | neutral | None | None | None | None | N |
| H/N | 0.3167 | likely_benign | 0.2709 | benign | -0.07 | Destabilizing | 0.014 | N | 0.131 | neutral | N | 0.449234934 | None | None | N |
| H/P | 0.8782 | likely_pathogenic | 0.8708 | pathogenic | 0.25 | Stabilizing | 0.99 | D | 0.539 | neutral | N | 0.502866807 | None | None | N |
| H/Q | 0.4936 | ambiguous | 0.4552 | ambiguous | 0.124 | Stabilizing | 0.942 | D | 0.443 | neutral | N | 0.491812275 | None | None | N |
| H/R | 0.174 | likely_benign | 0.1681 | benign | -0.699 | Destabilizing | 0.942 | D | 0.421 | neutral | N | 0.454061964 | None | None | N |
| H/S | 0.6413 | likely_pathogenic | 0.5823 | pathogenic | -0.081 | Destabilizing | 0.754 | D | 0.401 | neutral | None | None | None | None | N |
| H/T | 0.7853 | likely_pathogenic | 0.7031 | pathogenic | 0.091 | Stabilizing | 0.956 | D | 0.422 | neutral | None | None | None | None | N |
| H/V | 0.7148 | likely_pathogenic | 0.6351 | pathogenic | 0.25 | Stabilizing | 0.978 | D | 0.566 | neutral | None | None | None | None | N |
| H/W | 0.7092 | likely_pathogenic | 0.6754 | pathogenic | 0.7 | Stabilizing | 0.998 | D | 0.598 | neutral | None | None | None | None | N |
| H/Y | 0.2678 | likely_benign | 0.2445 | benign | 0.909 | Stabilizing | 0.966 | D | 0.463 | neutral | N | 0.485016041 | 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.