Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1145 | 3658;3659;3660 | chr2:178781211;178781210;178781209 | chr2:179645938;179645937;179645936 |
| N2AB | 1145 | 3658;3659;3660 | chr2:178781211;178781210;178781209 | chr2:179645938;179645937;179645936 |
| N2A | 1145 | 3658;3659;3660 | chr2:178781211;178781210;178781209 | chr2:179645938;179645937;179645936 |
| N2B | 1099 | 3520;3521;3522 | chr2:178781211;178781210;178781209 | chr2:179645938;179645937;179645936 |
| Novex-1 | 1099 | 3520;3521;3522 | chr2:178781211;178781210;178781209 | chr2:179645938;179645937;179645936 |
| Novex-2 | 1099 | 3520;3521;3522 | chr2:178781211;178781210;178781209 | chr2:179645938;179645937;179645936 |
| Novex-3 | 1145 | 3658;3659;3660 | chr2:178781211;178781210;178781209 | chr2:179645938;179645937;179645936 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/T | rs1006970338  |
0.629 | 0.994 | N | 0.507 | 0.553 | 0.659878960944 | gnomAD-2.1.1 | 7.96E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.45E-05 | None | 0 | None | 0 | 8.81E-06 | 0 |
| M/T | rs1006970338 |
0.629 | 0.994 | N | 0.507 | 0.553 | 0.659878960944 | gnomAD-4.0.0 | 4.7723E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.71367E-06 | 0 | 3.02206E-05 |
| M/V | rs2092731839 |
None | 0.985 | N | 0.463 | 0.33 | 0.411001663086 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/V | rs2092731839 |
None | 0.985 | N | 0.463 | 0.33 | 0.411001663086 | gnomAD-4.0.0 | 2.5613E-06 | None | None | None | None | I | None | 1.69027E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.39197E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.9051 | likely_pathogenic | 0.8719 | pathogenic | -0.632 | Destabilizing | 0.989 | D | 0.519 | neutral | None | None | None | None | I |
| M/C | 0.9669 | likely_pathogenic | 0.9561 | pathogenic | -0.751 | Destabilizing | 1.0 | D | 0.503 | neutral | None | None | None | None | I |
| M/D | 0.9863 | likely_pathogenic | 0.9804 | pathogenic | 0.878 | Stabilizing | 0.999 | D | 0.633 | neutral | None | None | None | None | I |
| M/E | 0.9455 | likely_pathogenic | 0.92 | pathogenic | 0.887 | Stabilizing | 0.999 | D | 0.493 | neutral | None | None | None | None | I |
| M/F | 0.7772 | likely_pathogenic | 0.741 | pathogenic | -0.003 | Destabilizing | 0.999 | D | 0.438 | neutral | None | None | None | None | I |
| M/G | 0.9625 | likely_pathogenic | 0.9412 | pathogenic | -0.888 | Destabilizing | 0.995 | D | 0.541 | neutral | None | None | None | None | I |
| M/H | 0.9418 | likely_pathogenic | 0.9276 | pathogenic | -0.056 | Destabilizing | 1.0 | D | 0.598 | neutral | None | None | None | None | I |
| M/I | 0.9609 | likely_pathogenic | 0.9515 | pathogenic | -0.028 | Destabilizing | 0.985 | D | 0.538 | neutral | N | 0.440753386 | None | None | I |
| M/K | 0.8703 | likely_pathogenic | 0.8477 | pathogenic | 0.588 | Stabilizing | 0.994 | D | 0.509 | neutral | N | 0.34909235 | None | None | I |
| M/L | 0.4822 | ambiguous | 0.4029 | ambiguous | -0.028 | Destabilizing | 0.927 | D | 0.327 | neutral | N | 0.440297767 | None | None | I |
| M/N | 0.9123 | likely_pathogenic | 0.8919 | pathogenic | 0.634 | Stabilizing | 0.999 | D | 0.586 | neutral | None | None | None | None | I |
| M/P | 0.994 | likely_pathogenic | 0.9926 | pathogenic | -0.199 | Destabilizing | 0.999 | D | 0.586 | neutral | None | None | None | None | I |
| M/Q | 0.8178 | likely_pathogenic | 0.771 | pathogenic | 0.594 | Stabilizing | 0.999 | D | 0.437 | neutral | None | None | None | None | I |
| M/R | 0.8626 | likely_pathogenic | 0.8257 | pathogenic | 0.844 | Stabilizing | 0.998 | D | 0.455 | neutral | N | 0.359118054 | None | None | I |
| M/S | 0.89 | likely_pathogenic | 0.8622 | pathogenic | -0.016 | Destabilizing | 0.995 | D | 0.489 | neutral | None | None | None | None | I |
| M/T | 0.8995 | likely_pathogenic | 0.8782 | pathogenic | 0.119 | Stabilizing | 0.994 | D | 0.507 | neutral | N | 0.40259392 | None | None | I |
| M/V | 0.4755 | ambiguous | 0.4441 | ambiguous | -0.199 | Destabilizing | 0.985 | D | 0.463 | neutral | N | 0.423785273 | None | None | I |
| M/W | 0.9711 | likely_pathogenic | 0.9603 | pathogenic | 0.023 | Stabilizing | 1.0 | D | 0.543 | neutral | None | None | None | None | I |
| M/Y | 0.9282 | likely_pathogenic | 0.9059 | pathogenic | 0.175 | Stabilizing | 0.999 | D | 0.491 | 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.