Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17284 | 52075;52076;52077 | chr2:178609460;178609459;178609458 | chr2:179474187;179474186;179474185 |
| N2AB | 15643 | 47152;47153;47154 | chr2:178609460;178609459;178609458 | chr2:179474187;179474186;179474185 |
| N2A | 14716 | 44371;44372;44373 | chr2:178609460;178609459;178609458 | chr2:179474187;179474186;179474185 |
| N2B | 8219 | 24880;24881;24882 | chr2:178609460;178609459;178609458 | chr2:179474187;179474186;179474185 |
| Novex-1 | 8344 | 25255;25256;25257 | chr2:178609460;178609459;178609458 | chr2:179474187;179474186;179474185 |
| Novex-2 | 8411 | 25456;25457;25458 | chr2:178609460;178609459;178609458 | chr2:179474187;179474186;179474185 |
| 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 | None | None | 0.625 | N | 0.488 | 0.135 | 0.285316908763 | gnomAD-4.0.0 | 1.36947E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.53357E-05 | None | 0 | 0 | 8.9992E-07 | 0 | 0 |
| D/N | None | None | 0.002 | N | 0.228 | 0.135 | 0.16115917748 | gnomAD-4.0.0 | 6.84735E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99923E-07 | 0 | 0 |
| D/Y | rs1309961194  |
-0.339 | 0.989 | N | 0.665 | 0.416 | 0.512707719942 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| D/Y | rs1309961194 |
-0.339 | 0.989 | N | 0.665 | 0.416 | 0.512707719942 | gnomAD-4.0.0 | 7.53208E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.89915E-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 | 0.4011 | ambiguous | 0.3749 | ambiguous | -0.525 | Destabilizing | 0.801 | D | 0.574 | neutral | N | 0.509816459 | None | None | N |
| D/C | 0.8094 | likely_pathogenic | 0.8031 | pathogenic | -0.15 | Destabilizing | 0.998 | D | 0.668 | neutral | None | None | None | None | N |
| D/E | 0.2867 | likely_benign | 0.2851 | benign | -0.444 | Destabilizing | 0.625 | D | 0.488 | neutral | N | 0.482205783 | None | None | N |
| D/F | 0.8589 | likely_pathogenic | 0.8395 | pathogenic | -0.263 | Destabilizing | 0.991 | D | 0.665 | neutral | None | None | None | None | N |
| D/G | 0.1431 | likely_benign | 0.1332 | benign | -0.795 | Destabilizing | 0.454 | N | 0.483 | neutral | N | 0.473815587 | None | None | N |
| D/H | 0.5666 | likely_pathogenic | 0.5493 | ambiguous | -0.345 | Destabilizing | 0.966 | D | 0.58 | neutral | N | 0.488540625 | None | None | N |
| D/I | 0.8681 | likely_pathogenic | 0.8346 | pathogenic | 0.163 | Stabilizing | 0.974 | D | 0.657 | neutral | None | None | None | None | N |
| D/K | 0.6055 | likely_pathogenic | 0.5659 | pathogenic | -0.084 | Destabilizing | 0.842 | D | 0.522 | neutral | None | None | None | None | N |
| D/L | 0.7277 | likely_pathogenic | 0.6949 | pathogenic | 0.163 | Stabilizing | 0.974 | D | 0.624 | neutral | None | None | None | None | N |
| D/M | 0.861 | likely_pathogenic | 0.8435 | pathogenic | 0.433 | Stabilizing | 0.998 | D | 0.647 | neutral | None | None | None | None | N |
| D/N | 0.1103 | likely_benign | 0.1119 | benign | -0.469 | Destabilizing | 0.002 | N | 0.228 | neutral | N | 0.426058925 | None | None | N |
| D/P | 0.9621 | likely_pathogenic | 0.9435 | pathogenic | -0.043 | Destabilizing | 0.991 | D | 0.571 | neutral | None | None | None | None | N |
| D/Q | 0.5676 | likely_pathogenic | 0.5542 | ambiguous | -0.384 | Destabilizing | 0.974 | D | 0.543 | neutral | None | None | None | None | N |
| D/R | 0.6577 | likely_pathogenic | 0.6182 | pathogenic | 0.109 | Stabilizing | 0.949 | D | 0.609 | neutral | None | None | None | None | N |
| D/S | 0.2556 | likely_benign | 0.2502 | benign | -0.621 | Destabilizing | 0.525 | D | 0.523 | neutral | None | None | None | None | N |
| D/T | 0.6801 | likely_pathogenic | 0.6459 | pathogenic | -0.407 | Destabilizing | 0.842 | D | 0.531 | neutral | None | None | None | None | N |
| D/V | 0.6924 | likely_pathogenic | 0.6379 | pathogenic | -0.043 | Destabilizing | 0.966 | D | 0.635 | neutral | N | 0.477437809 | None | None | N |
| D/W | 0.9473 | likely_pathogenic | 0.9355 | pathogenic | -0.072 | Destabilizing | 0.998 | D | 0.664 | neutral | None | None | None | None | N |
| D/Y | 0.4492 | ambiguous | 0.4096 | ambiguous | -0.029 | Destabilizing | 0.989 | D | 0.665 | neutral | N | 0.488794114 | 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.