Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2543 | 7852;7853;7854 | chr2:178773337;178773336;178773335 | chr2:179638064;179638063;179638062 |
| N2AB | 2543 | 7852;7853;7854 | chr2:178773337;178773336;178773335 | chr2:179638064;179638063;179638062 |
| N2A | 2543 | 7852;7853;7854 | chr2:178773337;178773336;178773335 | chr2:179638064;179638063;179638062 |
| N2B | 2497 | 7714;7715;7716 | chr2:178773337;178773336;178773335 | chr2:179638064;179638063;179638062 |
| Novex-1 | 2497 | 7714;7715;7716 | chr2:178773337;178773336;178773335 | chr2:179638064;179638063;179638062 |
| Novex-2 | 2497 | 7714;7715;7716 | chr2:178773337;178773336;178773335 | chr2:179638064;179638063;179638062 |
| Novex-3 | 2543 | 7852;7853;7854 | chr2:178773337;178773336;178773335 | chr2:179638064;179638063;179638062 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs765136135  |
-0.061 | 0.852 | N | 0.339 | 0.405 | 0.468420198123 | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | N | None | 1.22289E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/I | rs765136135 |
-0.061 | 0.852 | N | 0.339 | 0.405 | 0.468420198123 | gnomAD-3.1.2 | 3.94E-05 | None | None | None | None | N | None | 1.20761E-04 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/I | rs765136135 |
-0.061 | 0.852 | N | 0.339 | 0.405 | 0.468420198123 | gnomAD-4.0.0 | 6.19647E-06 | None | None | None | None | N | None | 1.20196E-04 | 1.66739E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/N | None | None | 0.976 | D | 0.356 | 0.313 | 0.461495907335 | gnomAD-4.0.0 | 3.42066E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.49659E-06 | 0 | 0 |
| T/S | rs765136135 |
-0.649 | 0.31 | N | 0.171 | 0.238 | 0.277317399466 | gnomAD-2.1.1 | 2.84E-05 | None | None | None | None | N | None | 3.26105E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/S | rs765136135 |
-0.649 | 0.31 | N | 0.171 | 0.238 | 0.277317399466 | gnomAD-3.1.2 | 8.55E-05 | None | None | None | None | N | None | 3.13979E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/S | rs765136135 |
-0.649 | 0.31 | N | 0.171 | 0.238 | 0.277317399466 | gnomAD-4.0.0 | 4.77248E-06 | None | None | None | None | N | None | 0 | 2.28707E-05 | None | 0 | 0 | None | 0 | 0 | 5.71337E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1078 | likely_benign | 0.1122 | benign | -0.274 | Destabilizing | 0.704 | D | 0.369 | neutral | D | 0.554679116 | None | None | N |
| T/C | 0.4895 | ambiguous | 0.5237 | ambiguous | -0.302 | Destabilizing | 0.999 | D | 0.473 | neutral | None | None | None | None | N |
| T/D | 0.3753 | ambiguous | 0.3921 | ambiguous | 0.274 | Stabilizing | 0.939 | D | 0.396 | neutral | None | None | None | None | N |
| T/E | 0.2612 | likely_benign | 0.2638 | benign | 0.203 | Stabilizing | 0.939 | D | 0.385 | neutral | None | None | None | None | N |
| T/F | 0.2509 | likely_benign | 0.2695 | benign | -0.771 | Destabilizing | 0.991 | D | 0.513 | neutral | None | None | None | None | N |
| T/G | 0.367 | ambiguous | 0.3883 | ambiguous | -0.402 | Destabilizing | 0.939 | D | 0.406 | neutral | None | None | None | None | N |
| T/H | 0.2193 | likely_benign | 0.2236 | benign | -0.651 | Destabilizing | 0.999 | D | 0.507 | neutral | None | None | None | None | N |
| T/I | 0.1576 | likely_benign | 0.1609 | benign | -0.059 | Destabilizing | 0.852 | D | 0.339 | neutral | N | 0.514246674 | None | None | N |
| T/K | 0.1947 | likely_benign | 0.1871 | benign | -0.299 | Destabilizing | 0.939 | D | 0.389 | neutral | None | None | None | None | N |
| T/L | 0.1303 | likely_benign | 0.1312 | benign | -0.059 | Destabilizing | 0.759 | D | 0.352 | neutral | None | None | None | None | N |
| T/M | 0.1299 | likely_benign | 0.1312 | benign | -0.024 | Destabilizing | 0.991 | D | 0.468 | neutral | None | None | None | None | N |
| T/N | 0.1287 | likely_benign | 0.1315 | benign | -0.13 | Destabilizing | 0.976 | D | 0.356 | neutral | D | 0.541165782 | None | None | N |
| T/P | 0.1808 | likely_benign | 0.1795 | benign | -0.101 | Destabilizing | 0.988 | D | 0.431 | neutral | D | 0.624679224 | None | None | N |
| T/Q | 0.211 | likely_benign | 0.2086 | benign | -0.321 | Destabilizing | 0.991 | D | 0.462 | neutral | None | None | None | None | N |
| T/R | 0.1652 | likely_benign | 0.1602 | benign | -0.046 | Destabilizing | 0.991 | D | 0.444 | neutral | None | None | None | None | N |
| T/S | 0.12 | likely_benign | 0.1232 | benign | -0.338 | Destabilizing | 0.31 | N | 0.171 | neutral | N | 0.509023002 | None | None | N |
| T/V | 0.1447 | likely_benign | 0.1534 | benign | -0.101 | Destabilizing | 0.079 | N | 0.119 | neutral | None | None | None | None | N |
| T/W | 0.6467 | likely_pathogenic | 0.6649 | pathogenic | -0.802 | Destabilizing | 0.999 | D | 0.614 | neutral | None | None | None | None | N |
| T/Y | 0.2924 | likely_benign | 0.3084 | benign | -0.5 | Destabilizing | 0.997 | D | 0.509 | 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.