Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15255 | 45988;45989;45990 | chr2:178620847;178620846;178620845 | chr2:179485574;179485573;179485572 |
| N2AB | 13614 | 41065;41066;41067 | chr2:178620847;178620846;178620845 | chr2:179485574;179485573;179485572 |
| N2A | 12687 | 38284;38285;38286 | chr2:178620847;178620846;178620845 | chr2:179485574;179485573;179485572 |
| N2B | 6190 | 18793;18794;18795 | chr2:178620847;178620846;178620845 | chr2:179485574;179485573;179485572 |
| Novex-1 | 6315 | 19168;19169;19170 | chr2:178620847;178620846;178620845 | chr2:179485574;179485573;179485572 |
| Novex-2 | 6382 | 19369;19370;19371 | chr2:178620847;178620846;178620845 | chr2:179485574;179485573;179485572 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/F | None | None | 0.81 | N | 0.477 | 0.31 | 0.648717662934 | gnomAD-4.0.0 | 1.59355E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86252E-06 | 0 | 0 |
| I/T | rs746579432  |
-2.259 | 0.549 | N | 0.449 | 0.411 | 0.741748209757 | gnomAD-2.1.1 | 8.08E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.79E-05 | 0 |
| I/T | rs746579432 |
-2.259 | 0.549 | N | 0.449 | 0.411 | 0.741748209757 | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 9.42E-05 | 0 | 0 | 0 | 0 |
| I/T | rs746579432 |
-2.259 | 0.549 | N | 0.449 | 0.411 | 0.741748209757 | gnomAD-4.0.0 | 5.1329E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 1.56917E-05 | 0 | 4.7937E-06 | 0 | 2.84981E-05 |
| I/V | None | None | 0.002 | N | 0.126 | 0.092 | 0.490976584422 | gnomAD-4.0.0 | 1.59355E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86252E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.6567 | likely_pathogenic | 0.7631 | pathogenic | -2.065 | Highly Destabilizing | 0.25 | N | 0.373 | neutral | None | None | None | None | I |
| I/C | 0.8326 | likely_pathogenic | 0.8683 | pathogenic | -1.23 | Destabilizing | 0.992 | D | 0.485 | neutral | None | None | None | None | I |
| I/D | 0.9433 | likely_pathogenic | 0.9656 | pathogenic | -1.848 | Destabilizing | 0.972 | D | 0.601 | neutral | None | None | None | None | I |
| I/E | 0.9041 | likely_pathogenic | 0.9371 | pathogenic | -1.675 | Destabilizing | 0.92 | D | 0.588 | neutral | None | None | None | None | I |
| I/F | 0.1721 | likely_benign | 0.2479 | benign | -1.232 | Destabilizing | 0.81 | D | 0.477 | neutral | N | 0.51115238 | None | None | I |
| I/G | 0.8892 | likely_pathogenic | 0.9315 | pathogenic | -2.557 | Highly Destabilizing | 0.92 | D | 0.581 | neutral | None | None | None | None | I |
| I/H | 0.7258 | likely_pathogenic | 0.8167 | pathogenic | -1.885 | Destabilizing | 0.992 | D | 0.591 | neutral | None | None | None | None | I |
| I/K | 0.7201 | likely_pathogenic | 0.8111 | pathogenic | -1.497 | Destabilizing | 0.92 | D | 0.584 | neutral | None | None | None | None | I |
| I/L | 0.1322 | likely_benign | 0.169 | benign | -0.691 | Destabilizing | 0.016 | N | 0.279 | neutral | N | 0.510049764 | None | None | I |
| I/M | 0.1107 | likely_benign | 0.1521 | benign | -0.528 | Destabilizing | 0.02 | N | 0.125 | neutral | N | 0.438395409 | None | None | I |
| I/N | 0.582 | likely_pathogenic | 0.6972 | pathogenic | -1.679 | Destabilizing | 0.963 | D | 0.609 | neutral | D | 0.601758781 | None | None | I |
| I/P | 0.9152 | likely_pathogenic | 0.9446 | pathogenic | -1.125 | Destabilizing | 0.972 | D | 0.603 | neutral | None | None | None | None | I |
| I/Q | 0.7294 | likely_pathogenic | 0.8048 | pathogenic | -1.604 | Destabilizing | 0.92 | D | 0.603 | neutral | None | None | None | None | I |
| I/R | 0.6105 | likely_pathogenic | 0.7139 | pathogenic | -1.171 | Destabilizing | 0.92 | D | 0.604 | neutral | None | None | None | None | I |
| I/S | 0.5646 | likely_pathogenic | 0.6626 | pathogenic | -2.389 | Highly Destabilizing | 0.549 | D | 0.497 | neutral | D | 0.558103842 | None | None | I |
| I/T | 0.463 | ambiguous | 0.5748 | pathogenic | -2.071 | Highly Destabilizing | 0.549 | D | 0.449 | neutral | N | 0.515989177 | None | None | I |
| I/V | 0.1138 | likely_benign | 0.1427 | benign | -1.125 | Destabilizing | 0.002 | N | 0.126 | neutral | N | 0.494613501 | None | None | I |
| I/W | 0.8606 | likely_pathogenic | 0.9069 | pathogenic | -1.539 | Destabilizing | 0.992 | D | 0.616 | neutral | None | None | None | None | I |
| I/Y | 0.624 | likely_pathogenic | 0.7192 | pathogenic | -1.216 | Destabilizing | 0.92 | D | 0.505 | 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.