Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14928 | 45007;45008;45009 | chr2:178624498;178624497;178624496 | chr2:179489225;179489224;179489223 |
| N2AB | 13287 | 40084;40085;40086 | chr2:178624498;178624497;178624496 | chr2:179489225;179489224;179489223 |
| N2A | 12360 | 37303;37304;37305 | chr2:178624498;178624497;178624496 | chr2:179489225;179489224;179489223 |
| N2B | 5863 | 17812;17813;17814 | chr2:178624498;178624497;178624496 | chr2:179489225;179489224;179489223 |
| Novex-1 | 5988 | 18187;18188;18189 | chr2:178624498;178624497;178624496 | chr2:179489225;179489224;179489223 |
| Novex-2 | 6055 | 18388;18389;18390 | chr2:178624498;178624497;178624496 | chr2:179489225;179489224;179489223 |
| 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/N | rs772700762  |
-0.243 | 0.961 | N | 0.36 | 0.211 | 0.183819452728 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| D/N | rs772700762 |
-0.243 | 0.961 | N | 0.36 | 0.211 | 0.183819452728 | gnomAD-4.0.0 | 1.59389E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86351E-06 | 0 | 0 |
| D/V | rs2058743726 |
None | 0.994 | N | 0.58 | 0.252 | 0.218845423259 | gnomAD-4.0.0 | 6.84692E-07 | None | None | None | None | N | None | 2.99509E-05 | 0 | None | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.3383 | likely_benign | 0.329 | benign | -0.19 | Destabilizing | 0.925 | D | 0.406 | neutral | N | 0.324329357 | None | None | N |
| D/C | 0.8527 | likely_pathogenic | 0.8555 | pathogenic | -0.253 | Destabilizing | 1.0 | D | 0.633 | neutral | None | None | None | None | N |
| D/E | 0.3231 | likely_benign | 0.309 | benign | -0.323 | Destabilizing | 0.248 | N | 0.208 | neutral | N | 0.341967733 | None | None | N |
| D/F | 0.8028 | likely_pathogenic | 0.7832 | pathogenic | 0.006 | Stabilizing | 0.996 | D | 0.571 | neutral | None | None | None | None | N |
| D/G | 0.2403 | likely_benign | 0.228 | benign | -0.371 | Destabilizing | 0.961 | D | 0.334 | neutral | N | 0.336957644 | None | None | N |
| D/H | 0.5138 | ambiguous | 0.5368 | ambiguous | 0.505 | Stabilizing | 0.29 | N | 0.277 | neutral | N | 0.348359408 | None | None | N |
| D/I | 0.614 | likely_pathogenic | 0.5943 | pathogenic | 0.239 | Stabilizing | 0.996 | D | 0.573 | neutral | None | None | None | None | N |
| D/K | 0.6103 | likely_pathogenic | 0.6465 | pathogenic | 0.353 | Stabilizing | 0.97 | D | 0.324 | neutral | None | None | None | None | N |
| D/L | 0.6598 | likely_pathogenic | 0.6456 | pathogenic | 0.239 | Stabilizing | 0.996 | D | 0.577 | neutral | None | None | None | None | N |
| D/M | 0.8426 | likely_pathogenic | 0.8251 | pathogenic | 0.089 | Stabilizing | 1.0 | D | 0.597 | neutral | None | None | None | None | N |
| D/N | 0.1601 | likely_benign | 0.159 | benign | -0.137 | Destabilizing | 0.961 | D | 0.36 | neutral | N | 0.341535858 | None | None | N |
| D/P | 0.8524 | likely_pathogenic | 0.8982 | pathogenic | 0.117 | Stabilizing | 0.999 | D | 0.365 | neutral | None | None | None | None | N |
| D/Q | 0.5851 | likely_pathogenic | 0.5929 | pathogenic | -0.082 | Destabilizing | 0.991 | D | 0.321 | neutral | None | None | None | None | N |
| D/R | 0.6623 | likely_pathogenic | 0.6821 | pathogenic | 0.673 | Stabilizing | 0.991 | D | 0.498 | neutral | None | None | None | None | N |
| D/S | 0.2726 | likely_benign | 0.2615 | benign | -0.205 | Destabilizing | 0.746 | D | 0.179 | neutral | None | None | None | None | N |
| D/T | 0.445 | ambiguous | 0.4257 | ambiguous | -0.048 | Destabilizing | 0.97 | D | 0.319 | neutral | None | None | None | None | N |
| D/V | 0.4314 | ambiguous | 0.3972 | ambiguous | 0.117 | Stabilizing | 0.994 | D | 0.58 | neutral | N | 0.334771951 | None | None | N |
| D/W | 0.9494 | likely_pathogenic | 0.949 | pathogenic | 0.162 | Stabilizing | 1.0 | D | 0.663 | neutral | None | None | None | None | N |
| D/Y | 0.347 | ambiguous | 0.3361 | benign | 0.257 | Stabilizing | 0.989 | D | 0.575 | neutral | N | 0.412290621 | 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.