Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 34322 | 103189;103190;103191 | chr2:178533651;178533650;178533649 | chr2:179398378;179398377;179398376 |
| N2AB | 32681 | 98266;98267;98268 | chr2:178533651;178533650;178533649 | chr2:179398378;179398377;179398376 |
| N2A | 31754 | 95485;95486;95487 | chr2:178533651;178533650;178533649 | chr2:179398378;179398377;179398376 |
| N2B | 25257 | 75994;75995;75996 | chr2:178533651;178533650;178533649 | chr2:179398378;179398377;179398376 |
| Novex-1 | 25382 | 76369;76370;76371 | chr2:178533651;178533650;178533649 | chr2:179398378;179398377;179398376 |
| Novex-2 | 25449 | 76570;76571;76572 | chr2:178533651;178533650;178533649 | chr2:179398378;179398377;179398376 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/N | rs763242057  |
-0.911 | None | N | 0.12 | 0.062 | 0.0482279557977 | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.64E-05 | 3.55E-05 | 0 |
| S/N | rs763242057 |
-0.911 | None | N | 0.12 | 0.062 | 0.0482279557977 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 9.42E-05 | 0 | 2.94E-05 | 0 | 0 |
| S/N | rs763242057 |
-0.911 | None | N | 0.12 | 0.062 | 0.0482279557977 | gnomAD-4.0.0 | 2.72646E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.1251E-05 | 0 | 3.47496E-05 | 0 | 1.60097E-05 |
| S/R | None | None | 0.029 | N | 0.414 | 0.211 | 0.0482279557977 | gnomAD-4.0.0 | 1.59102E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43279E-05 | 0 |
| S/T | rs763242057 |
-0.751 | 0.012 | N | 0.395 | 0.037 | 0.0716867268079 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.86E-06 | 0 |
| S/T | rs763242057 |
-0.751 | 0.012 | N | 0.395 | 0.037 | 0.0716867268079 | gnomAD-4.0.0 | 6.84165E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99412E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1004 | likely_benign | 0.0883 | benign | -0.512 | Destabilizing | 0.031 | N | 0.371 | neutral | None | None | None | None | N |
| S/C | 0.1128 | likely_benign | 0.1223 | benign | -0.31 | Destabilizing | 0.828 | D | 0.413 | neutral | N | 0.43762236 | None | None | N |
| S/D | 0.1424 | likely_benign | 0.159 | benign | -0.429 | Destabilizing | 0.016 | N | 0.367 | neutral | None | None | None | None | N |
| S/E | 0.2991 | likely_benign | 0.2882 | benign | -0.513 | Destabilizing | 0.016 | N | 0.373 | neutral | None | None | None | None | N |
| S/F | 0.3382 | likely_benign | 0.2818 | benign | -1.113 | Destabilizing | 0.628 | D | 0.481 | neutral | None | None | None | None | N |
| S/G | 0.0846 | likely_benign | 0.0871 | benign | -0.636 | Destabilizing | 0.012 | N | 0.372 | neutral | N | 0.435608623 | None | None | N |
| S/H | 0.1544 | likely_benign | 0.1729 | benign | -1.236 | Destabilizing | 0.214 | N | 0.429 | neutral | None | None | None | None | N |
| S/I | 0.277 | likely_benign | 0.2829 | benign | -0.309 | Destabilizing | 0.295 | N | 0.458 | neutral | N | 0.444205726 | None | None | N |
| S/K | 0.2921 | likely_benign | 0.3217 | benign | -0.578 | Destabilizing | None | N | 0.105 | neutral | None | None | None | None | N |
| S/L | 0.1755 | likely_benign | 0.1434 | benign | -0.309 | Destabilizing | 0.072 | N | 0.411 | neutral | None | None | None | None | N |
| S/M | 0.2542 | likely_benign | 0.221 | benign | 0.211 | Stabilizing | 0.628 | D | 0.424 | neutral | None | None | None | None | N |
| S/N | 0.0637 | likely_benign | 0.0721 | benign | -0.39 | Destabilizing | None | N | 0.12 | neutral | N | 0.358009057 | None | None | N |
| S/P | 0.7161 | likely_pathogenic | 0.6685 | pathogenic | -0.349 | Destabilizing | 0.136 | N | 0.412 | neutral | None | None | None | None | N |
| S/Q | 0.263 | likely_benign | 0.2691 | benign | -0.748 | Destabilizing | 0.072 | N | 0.342 | neutral | None | None | None | None | N |
| S/R | 0.2448 | likely_benign | 0.2856 | benign | -0.298 | Destabilizing | 0.029 | N | 0.414 | neutral | N | 0.411443684 | None | None | N |
| S/T | 0.1067 | likely_benign | 0.0993 | benign | -0.458 | Destabilizing | 0.012 | N | 0.395 | neutral | N | 0.460160351 | None | None | N |
| S/V | 0.2942 | likely_benign | 0.2815 | benign | -0.349 | Destabilizing | 0.136 | N | 0.419 | neutral | None | None | None | None | N |
| S/W | 0.423 | ambiguous | 0.4151 | ambiguous | -1.082 | Destabilizing | 0.864 | D | 0.525 | neutral | None | None | None | None | N |
| S/Y | 0.1908 | likely_benign | 0.1803 | benign | -0.809 | Destabilizing | 0.628 | D | 0.471 | 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.