Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16606 | 50041;50042;50043 | chr2:178612905;178612904;178612903 | chr2:179477632;179477631;179477630 |
| N2AB | 14965 | 45118;45119;45120 | chr2:178612905;178612904;178612903 | chr2:179477632;179477631;179477630 |
| N2A | 14038 | 42337;42338;42339 | chr2:178612905;178612904;178612903 | chr2:179477632;179477631;179477630 |
| N2B | 7541 | 22846;22847;22848 | chr2:178612905;178612904;178612903 | chr2:179477632;179477631;179477630 |
| Novex-1 | 7666 | 23221;23222;23223 | chr2:178612905;178612904;178612903 | chr2:179477632;179477631;179477630 |
| Novex-2 | 7733 | 23422;23423;23424 | chr2:178612905;178612904;178612903 | chr2:179477632;179477631;179477630 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/S | rs540303634  |
-0.487 | 0.817 | N | 0.286 | 0.197 | 0.176091768786 | gnomAD-2.1.1 | 2.42E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 3.39213E-04 | None | 0 | None | 0 | 0 | 0 |
| P/S | rs540303634 |
-0.487 | 0.817 | N | 0.286 | 0.197 | 0.176091768786 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 7.81555E-04 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | rs540303634 |
-0.487 | 0.817 | N | 0.286 | 0.197 | 0.176091768786 | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 2E-03 | 0 | None | None | None | 0 | None |
| P/S | rs540303634 |
-0.487 | 0.817 | N | 0.286 | 0.197 | 0.176091768786 | gnomAD-4.0.0 | 2.97672E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.0771E-03 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0911 | likely_benign | 0.0887 | benign | -0.406 | Destabilizing | 0.911 | D | 0.539 | neutral | N | 0.480306675 | None | None | N |
| P/C | 0.6144 | likely_pathogenic | 0.5822 | pathogenic | -0.791 | Destabilizing | 1.0 | D | 0.654 | neutral | None | None | None | None | N |
| P/D | 0.4628 | ambiguous | 0.54 | ambiguous | 0.088 | Stabilizing | 0.971 | D | 0.531 | neutral | None | None | None | None | N |
| P/E | 0.3018 | likely_benign | 0.3499 | ambiguous | -0.011 | Destabilizing | 0.985 | D | 0.534 | neutral | None | None | None | None | N |
| P/F | 0.5781 | likely_pathogenic | 0.5765 | pathogenic | -0.565 | Destabilizing | 0.998 | D | 0.642 | neutral | None | None | None | None | N |
| P/G | 0.3341 | likely_benign | 0.3432 | ambiguous | -0.524 | Destabilizing | 0.985 | D | 0.501 | neutral | None | None | None | None | N |
| P/H | 0.2411 | likely_benign | 0.2728 | benign | -0.04 | Destabilizing | 0.999 | D | 0.62 | neutral | N | 0.472784606 | None | None | N |
| P/I | 0.3559 | ambiguous | 0.3307 | benign | -0.242 | Destabilizing | 0.991 | D | 0.531 | neutral | None | None | None | None | N |
| P/K | 0.3086 | likely_benign | 0.3721 | ambiguous | -0.338 | Destabilizing | 0.985 | D | 0.53 | neutral | None | None | None | None | N |
| P/L | 0.1424 | likely_benign | 0.1351 | benign | -0.242 | Destabilizing | 0.961 | D | 0.532 | neutral | N | 0.473432305 | None | None | N |
| P/M | 0.3416 | ambiguous | 0.3124 | benign | -0.424 | Destabilizing | 0.999 | D | 0.62 | neutral | None | None | None | None | N |
| P/N | 0.3496 | ambiguous | 0.3368 | benign | -0.204 | Destabilizing | 0.671 | D | 0.339 | neutral | None | None | None | None | N |
| P/Q | 0.1698 | likely_benign | 0.1801 | benign | -0.379 | Destabilizing | 0.998 | D | 0.611 | neutral | None | None | None | None | N |
| P/R | 0.2208 | likely_benign | 0.2953 | benign | 0.096 | Stabilizing | 0.997 | D | 0.621 | neutral | N | 0.481119392 | None | None | N |
| P/S | 0.1335 | likely_benign | 0.1361 | benign | -0.618 | Destabilizing | 0.817 | D | 0.286 | neutral | N | 0.461825356 | None | None | N |
| P/T | 0.1142 | likely_benign | 0.1137 | benign | -0.609 | Destabilizing | 0.961 | D | 0.535 | neutral | N | 0.461236252 | None | None | N |
| P/V | 0.2304 | likely_benign | 0.218 | benign | -0.263 | Destabilizing | 0.671 | D | 0.329 | neutral | None | None | None | None | N |
| P/W | 0.7625 | likely_pathogenic | 0.8021 | pathogenic | -0.634 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | N |
| P/Y | 0.5521 | ambiguous | 0.5741 | pathogenic | -0.344 | Destabilizing | 0.999 | D | 0.639 | 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.