Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15223 | 45892;45893;45894 | chr2:178620943;178620942;178620941 | chr2:179485670;179485669;179485668 |
| N2AB | 13582 | 40969;40970;40971 | chr2:178620943;178620942;178620941 | chr2:179485670;179485669;179485668 |
| N2A | 12655 | 38188;38189;38190 | chr2:178620943;178620942;178620941 | chr2:179485670;179485669;179485668 |
| N2B | 6158 | 18697;18698;18699 | chr2:178620943;178620942;178620941 | chr2:179485670;179485669;179485668 |
| Novex-1 | 6283 | 19072;19073;19074 | chr2:178620943;178620942;178620941 | chr2:179485670;179485669;179485668 |
| Novex-2 | 6350 | 19273;19274;19275 | chr2:178620943;178620942;178620941 | chr2:179485670;179485669;179485668 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Q/E | None | None | 0.201 | N | 0.429 | 0.062 | 0.0986583533028 | gnomAD-4.0.0 | 6.84776E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.73913E-04 | 0 | 0 | 0 |
| Q/H | rs1261811728  |
-0.792 | 0.896 | N | 0.361 | 0.17 | 0.151104730317 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.65E-05 | 0 | 0 |
| Q/H | rs1261811728 |
-0.792 | 0.896 | N | 0.361 | 0.17 | 0.151104730317 | gnomAD-4.0.0 | 6.84763E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.87455E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Q/A | 0.3666 | ambiguous | 0.3399 | benign | -0.329 | Destabilizing | 0.447 | N | 0.377 | neutral | None | None | None | None | N |
| Q/C | 0.8598 | likely_pathogenic | 0.8384 | pathogenic | 0.118 | Stabilizing | 0.992 | D | 0.561 | neutral | None | None | None | None | N |
| Q/D | 0.4477 | ambiguous | 0.4068 | ambiguous | -0.111 | Destabilizing | 0.005 | N | 0.273 | neutral | None | None | None | None | N |
| Q/E | 0.0887 | likely_benign | 0.085 | benign | -0.1 | Destabilizing | 0.201 | N | 0.429 | neutral | N | 0.440430438 | None | None | N |
| Q/F | 0.8993 | likely_pathogenic | 0.8787 | pathogenic | -0.31 | Destabilizing | 0.972 | D | 0.498 | neutral | None | None | None | None | N |
| Q/G | 0.3836 | ambiguous | 0.3435 | ambiguous | -0.585 | Destabilizing | 0.617 | D | 0.419 | neutral | None | None | None | None | N |
| Q/H | 0.4232 | ambiguous | 0.4275 | ambiguous | -0.462 | Destabilizing | 0.896 | D | 0.361 | neutral | N | 0.438671612 | None | None | N |
| Q/I | 0.7069 | likely_pathogenic | 0.6589 | pathogenic | 0.276 | Stabilizing | 0.92 | D | 0.501 | neutral | None | None | None | None | N |
| Q/K | 0.1381 | likely_benign | 0.1249 | benign | -0.11 | Destabilizing | 0.004 | N | 0.261 | neutral | N | 0.437401208 | None | None | N |
| Q/L | 0.3352 | likely_benign | 0.2928 | benign | 0.276 | Stabilizing | 0.549 | D | 0.427 | neutral | D | 0.550445388 | None | None | N |
| Q/M | 0.5323 | ambiguous | 0.5007 | ambiguous | 0.542 | Stabilizing | 0.972 | D | 0.354 | neutral | None | None | None | None | N |
| Q/N | 0.4086 | ambiguous | 0.379 | ambiguous | -0.528 | Destabilizing | 0.617 | D | 0.398 | neutral | None | None | None | None | N |
| Q/P | 0.8117 | likely_pathogenic | 0.7406 | pathogenic | 0.104 | Stabilizing | 0.896 | D | 0.352 | neutral | D | 0.549002313 | None | None | N |
| Q/R | 0.181 | likely_benign | 0.1639 | benign | 0.027 | Stabilizing | 0.379 | N | 0.423 | neutral | N | 0.437611625 | None | None | N |
| Q/S | 0.429 | ambiguous | 0.3901 | ambiguous | -0.532 | Destabilizing | 0.447 | N | 0.393 | neutral | None | None | None | None | N |
| Q/T | 0.3576 | ambiguous | 0.323 | benign | -0.35 | Destabilizing | 0.617 | D | 0.389 | neutral | None | None | None | None | N |
| Q/V | 0.4992 | ambiguous | 0.4574 | ambiguous | 0.104 | Stabilizing | 0.85 | D | 0.406 | neutral | None | None | None | None | N |
| Q/W | 0.8199 | likely_pathogenic | 0.763 | pathogenic | -0.242 | Destabilizing | 0.992 | D | 0.598 | neutral | None | None | None | None | N |
| Q/Y | 0.7432 | likely_pathogenic | 0.714 | pathogenic | -0.014 | Destabilizing | 0.972 | D | 0.377 | 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.