Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28770 | 86533;86534;86535 | chr2:178559824;178559823;178559822 | chr2:179424551;179424550;179424549 |
| N2AB | 27129 | 81610;81611;81612 | chr2:178559824;178559823;178559822 | chr2:179424551;179424550;179424549 |
| N2A | 26202 | 78829;78830;78831 | chr2:178559824;178559823;178559822 | chr2:179424551;179424550;179424549 |
| N2B | 19705 | 59338;59339;59340 | chr2:178559824;178559823;178559822 | chr2:179424551;179424550;179424549 |
| Novex-1 | 19830 | 59713;59714;59715 | chr2:178559824;178559823;178559822 | chr2:179424551;179424550;179424549 |
| Novex-2 | 19897 | 59914;59915;59916 | chr2:178559824;178559823;178559822 | chr2:179424551;179424550;179424549 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/T | rs752764932  |
-0.707 | None | N | 0.156 | 0.106 | 0.0138822411134 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.28E-05 | None | 0 | 0 | 0 |
| A/T | rs752764932 |
-0.707 | None | N | 0.156 | 0.106 | 0.0138822411134 | gnomAD-4.0.0 | 3.19942E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86033E-06 | 1.43567E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.2515 | likely_benign | 0.2781 | benign | -0.829 | Destabilizing | 0.676 | D | 0.362 | neutral | None | None | None | None | N |
| A/D | 0.1678 | likely_benign | 0.1907 | benign | -0.41 | Destabilizing | 0.012 | N | 0.395 | neutral | N | 0.449047641 | None | None | N |
| A/E | 0.19 | likely_benign | 0.1959 | benign | -0.54 | Destabilizing | None | N | 0.265 | neutral | None | None | None | None | N |
| A/F | 0.2441 | likely_benign | 0.2577 | benign | -1.031 | Destabilizing | 0.356 | N | 0.433 | neutral | None | None | None | None | N |
| A/G | 0.083 | likely_benign | 0.0938 | benign | -0.603 | Destabilizing | None | N | 0.175 | neutral | N | 0.420805034 | None | None | N |
| A/H | 0.3392 | likely_benign | 0.3684 | ambiguous | -0.655 | Destabilizing | 0.356 | N | 0.421 | neutral | None | None | None | None | N |
| A/I | 0.202 | likely_benign | 0.2107 | benign | -0.407 | Destabilizing | 0.072 | N | 0.423 | neutral | None | None | None | None | N |
| A/K | 0.367 | ambiguous | 0.3953 | ambiguous | -0.664 | Destabilizing | 0.038 | N | 0.375 | neutral | None | None | None | None | N |
| A/L | 0.1417 | likely_benign | 0.1459 | benign | -0.407 | Destabilizing | 0.038 | N | 0.375 | neutral | None | None | None | None | N |
| A/M | 0.1577 | likely_benign | 0.1628 | benign | -0.358 | Destabilizing | 0.628 | D | 0.355 | neutral | None | None | None | None | N |
| A/N | 0.1391 | likely_benign | 0.1533 | benign | -0.354 | Destabilizing | 0.038 | N | 0.418 | neutral | None | None | None | None | N |
| A/P | 0.7621 | likely_pathogenic | 0.7723 | pathogenic | -0.401 | Destabilizing | 0.055 | N | 0.399 | neutral | N | 0.460198338 | None | None | N |
| A/Q | 0.2442 | likely_benign | 0.2545 | benign | -0.624 | Destabilizing | 0.038 | N | 0.399 | neutral | None | None | None | None | N |
| A/R | 0.3482 | ambiguous | 0.3799 | ambiguous | -0.248 | Destabilizing | 0.072 | N | 0.393 | neutral | None | None | None | None | N |
| A/S | 0.0656 | likely_benign | 0.0674 | benign | -0.645 | Destabilizing | None | N | 0.137 | neutral | N | 0.391828921 | None | None | N |
| A/T | 0.0652 | likely_benign | 0.0671 | benign | -0.685 | Destabilizing | None | N | 0.156 | neutral | N | 0.46988706 | None | None | N |
| A/V | 0.1108 | likely_benign | 0.1126 | benign | -0.401 | Destabilizing | 0.029 | N | 0.297 | neutral | N | 0.467964263 | None | None | N |
| A/W | 0.649 | likely_pathogenic | 0.6757 | pathogenic | -1.177 | Destabilizing | 0.864 | D | 0.461 | neutral | None | None | None | None | N |
| A/Y | 0.321 | likely_benign | 0.34 | benign | -0.806 | Destabilizing | 0.356 | N | 0.433 | 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.