Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13843 | 41752;41753;41754 | chr2:178636044;178636043;178636042 | chr2:179500771;179500770;179500769 |
| N2AB | 12202 | 36829;36830;36831 | chr2:178636044;178636043;178636042 | chr2:179500771;179500770;179500769 |
| N2A | 11275 | 34048;34049;34050 | chr2:178636044;178636043;178636042 | chr2:179500771;179500770;179500769 |
| N2B | 4778 | 14557;14558;14559 | chr2:178636044;178636043;178636042 | chr2:179500771;179500770;179500769 |
| Novex-1 | 4903 | 14932;14933;14934 | chr2:178636044;178636043;178636042 | chr2:179500771;179500770;179500769 |
| Novex-2 | 4970 | 15133;15134;15135 | chr2:178636044;178636043;178636042 | chr2:179500771;179500770;179500769 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs767535967  |
-0.132 | 0.826 | N | 0.319 | 0.096 | 0.15556083564 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.6E-05 | None | 0 | None | 0 | 0 | 0 |
| D/E | rs767535967 |
-0.132 | 0.826 | N | 0.319 | 0.096 | 0.15556083564 | gnomAD-4.0.0 | 1.59236E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77901E-05 | None | 0 | 0 | 0 | 0 | 0 |
| D/G | rs1482431359 |
None | 0.826 | N | 0.277 | 0.139 | 0.19670166235 | gnomAD-4.0.0 | 3.1847E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.72069E-06 | 0 | 0 |
| D/H | None | None | 0.988 | N | 0.361 | 0.247 | 0.258283824007 | gnomAD-4.0.0 | 4.80129E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.25001E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2978 | likely_benign | 0.3648 | ambiguous | -0.004 | Destabilizing | 0.704 | D | 0.299 | neutral | N | 0.341239851 | None | None | N |
| D/C | 0.7853 | likely_pathogenic | 0.837 | pathogenic | 0.389 | Stabilizing | 0.999 | D | 0.441 | neutral | None | None | None | None | N |
| D/E | 0.3359 | likely_benign | 0.3845 | ambiguous | -0.406 | Destabilizing | 0.826 | D | 0.319 | neutral | N | 0.346677199 | None | None | N |
| D/F | 0.8209 | likely_pathogenic | 0.8706 | pathogenic | -0.348 | Destabilizing | 0.997 | D | 0.473 | neutral | None | None | None | None | N |
| D/G | 0.2513 | likely_benign | 0.3148 | benign | -0.219 | Destabilizing | 0.826 | D | 0.277 | neutral | N | 0.349042518 | None | None | N |
| D/H | 0.583 | likely_pathogenic | 0.6965 | pathogenic | -0.643 | Destabilizing | 0.988 | D | 0.361 | neutral | N | 0.337639146 | None | None | N |
| D/I | 0.6709 | likely_pathogenic | 0.7484 | pathogenic | 0.508 | Stabilizing | 0.982 | D | 0.533 | neutral | None | None | None | None | N |
| D/K | 0.6211 | likely_pathogenic | 0.7238 | pathogenic | 0.252 | Stabilizing | 0.17 | N | 0.22 | neutral | None | None | None | None | N |
| D/L | 0.5853 | likely_pathogenic | 0.6523 | pathogenic | 0.508 | Stabilizing | 0.939 | D | 0.427 | neutral | None | None | None | None | N |
| D/M | 0.7872 | likely_pathogenic | 0.8298 | pathogenic | 0.895 | Stabilizing | 0.999 | D | 0.439 | neutral | None | None | None | None | N |
| D/N | 0.1069 | likely_benign | 0.1266 | benign | 0.123 | Stabilizing | 0.061 | N | 0.14 | neutral | N | 0.34215096 | None | None | N |
| D/P | 0.9714 | likely_pathogenic | 0.9786 | pathogenic | 0.362 | Stabilizing | 0.991 | D | 0.409 | neutral | None | None | None | None | N |
| D/Q | 0.6087 | likely_pathogenic | 0.6963 | pathogenic | 0.163 | Stabilizing | 0.982 | D | 0.319 | neutral | None | None | None | None | N |
| D/R | 0.6839 | likely_pathogenic | 0.7912 | pathogenic | 0.151 | Stabilizing | 0.884 | D | 0.347 | neutral | None | None | None | None | N |
| D/S | 0.1409 | likely_benign | 0.1781 | benign | 0.002 | Stabilizing | 0.373 | N | 0.192 | neutral | None | None | None | None | N |
| D/T | 0.2835 | likely_benign | 0.3318 | benign | 0.159 | Stabilizing | 0.17 | N | 0.208 | neutral | None | None | None | None | N |
| D/V | 0.4231 | ambiguous | 0.5011 | ambiguous | 0.362 | Stabilizing | 0.92 | D | 0.433 | neutral | N | 0.343134771 | None | None | N |
| D/W | 0.9701 | likely_pathogenic | 0.9793 | pathogenic | -0.419 | Destabilizing | 0.999 | D | 0.541 | neutral | None | None | None | None | N |
| D/Y | 0.5305 | ambiguous | 0.6378 | pathogenic | -0.169 | Destabilizing | 0.996 | D | 0.475 | neutral | N | 0.331061515 | 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.