Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13801 | 41626;41627;41628 | chr2:178636170;178636169;178636168 | chr2:179500897;179500896;179500895 |
| N2AB | 12160 | 36703;36704;36705 | chr2:178636170;178636169;178636168 | chr2:179500897;179500896;179500895 |
| N2A | 11233 | 33922;33923;33924 | chr2:178636170;178636169;178636168 | chr2:179500897;179500896;179500895 |
| N2B | 4736 | 14431;14432;14433 | chr2:178636170;178636169;178636168 | chr2:179500897;179500896;179500895 |
| Novex-1 | 4861 | 14806;14807;14808 | chr2:178636170;178636169;178636168 | chr2:179500897;179500896;179500895 |
| Novex-2 | 4928 | 15007;15008;15009 | chr2:178636170;178636169;178636168 | chr2:179500897;179500896;179500895 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/G | None | None | 0.101 | N | 0.487 | 0.145 | 0.15556083564 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-06 | 0 | 0 |
| S/N | rs757590541  |
-0.688 | 0.001 | N | 0.334 | 0.054 | 0.0954503805726 | gnomAD-2.1.1 | 1.62E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.2668E-04 | None | 0 | None | 0 | 0 | 0 |
| S/N | rs757590541 |
-0.688 | 0.001 | N | 0.334 | 0.054 | 0.0954503805726 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.93949E-04 | None | 0 | 0 | 0 | 0 | 0 |
| S/N | rs757590541 |
-0.688 | 0.001 | N | 0.334 | 0.054 | 0.0954503805726 | gnomAD-4.0.0 | 3.8493E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 4.88329E-05 | None | 0 | 0 | 0 | 0 | 2.84787E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1849 | likely_benign | 0.2011 | benign | -0.701 | Destabilizing | 0.061 | N | 0.433 | neutral | None | None | None | None | N |
| S/C | 0.245 | likely_benign | 0.2772 | benign | -0.373 | Destabilizing | 0.978 | D | 0.561 | neutral | N | 0.344096086 | None | None | N |
| S/D | 0.798 | likely_pathogenic | 0.8838 | pathogenic | -0.477 | Destabilizing | 0.129 | N | 0.551 | neutral | None | None | None | None | N |
| S/E | 0.8305 | likely_pathogenic | 0.8849 | pathogenic | -0.421 | Destabilizing | 0.228 | N | 0.541 | neutral | None | None | None | None | N |
| S/F | 0.5745 | likely_pathogenic | 0.6436 | pathogenic | -0.663 | Destabilizing | 0.836 | D | 0.657 | prob.neutral | None | None | None | None | N |
| S/G | 0.2443 | likely_benign | 0.2908 | benign | -1.023 | Destabilizing | 0.101 | N | 0.487 | neutral | N | 0.332345076 | None | None | N |
| S/H | 0.624 | likely_pathogenic | 0.7112 | pathogenic | -1.502 | Destabilizing | 0.716 | D | 0.584 | neutral | None | None | None | None | N |
| S/I | 0.3779 | ambiguous | 0.4505 | ambiguous | 0.067 | Stabilizing | 0.351 | N | 0.613 | neutral | N | 0.350819512 | None | None | N |
| S/K | 0.9355 | likely_pathogenic | 0.9636 | pathogenic | -0.739 | Destabilizing | 0.129 | N | 0.555 | neutral | None | None | None | None | N |
| S/L | 0.2918 | likely_benign | 0.3109 | benign | 0.067 | Stabilizing | 0.129 | N | 0.544 | neutral | None | None | None | None | N |
| S/M | 0.419 | ambiguous | 0.4348 | ambiguous | 0.241 | Stabilizing | 0.94 | D | 0.573 | neutral | None | None | None | None | N |
| S/N | 0.2793 | likely_benign | 0.3532 | ambiguous | -0.811 | Destabilizing | 0.001 | N | 0.334 | neutral | N | 0.348342162 | None | None | N |
| S/P | 0.9377 | likely_pathogenic | 0.9629 | pathogenic | -0.153 | Destabilizing | 0.593 | D | 0.575 | neutral | None | None | None | None | N |
| S/Q | 0.7528 | likely_pathogenic | 0.7967 | pathogenic | -0.793 | Destabilizing | 0.418 | N | 0.569 | neutral | None | None | None | None | N |
| S/R | 0.8765 | likely_pathogenic | 0.9276 | pathogenic | -0.804 | Destabilizing | 0.351 | N | 0.555 | neutral | N | 0.351135552 | None | None | N |
| S/T | 0.1449 | likely_benign | 0.155 | benign | -0.709 | Destabilizing | 0.001 | N | 0.317 | neutral | N | 0.314583565 | None | None | N |
| S/V | 0.4336 | ambiguous | 0.4763 | ambiguous | -0.153 | Destabilizing | 0.264 | N | 0.577 | neutral | None | None | None | None | N |
| S/W | 0.7272 | likely_pathogenic | 0.7837 | pathogenic | -0.751 | Destabilizing | 0.983 | D | 0.628 | neutral | None | None | None | None | N |
| S/Y | 0.4606 | ambiguous | 0.5435 | ambiguous | -0.453 | Destabilizing | 0.94 | D | 0.659 | prob.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.