Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20105 | 60538;60539;60540 | chr2:178591412;178591411;178591410 | chr2:179456139;179456138;179456137 |
| N2AB | 18464 | 55615;55616;55617 | chr2:178591412;178591411;178591410 | chr2:179456139;179456138;179456137 |
| N2A | 17537 | 52834;52835;52836 | chr2:178591412;178591411;178591410 | chr2:179456139;179456138;179456137 |
| N2B | 11040 | 33343;33344;33345 | chr2:178591412;178591411;178591410 | chr2:179456139;179456138;179456137 |
| Novex-1 | 11165 | 33718;33719;33720 | chr2:178591412;178591411;178591410 | chr2:179456139;179456138;179456137 |
| Novex-2 | 11232 | 33919;33920;33921 | chr2:178591412;178591411;178591410 | chr2:179456139;179456138;179456137 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/G | rs727504490  |
-0.36 | 0.995 | N | 0.617 | 0.463 | 0.837754063024 | gnomAD-2.1.1 | 2.16E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.94E-05 | 1.41844E-04 |
| V/G | rs727504490 |
-0.36 | 0.995 | N | 0.617 | 0.463 | 0.837754063024 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 3.16456E-03 | 4.41E-05 | 0 | 0 |
| V/G | rs727504490 |
-0.36 | 0.995 | N | 0.617 | 0.463 | 0.837754063024 | gnomAD-4.0.0 | 2.54463E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.65673E-03 | 2.37567E-05 | 1.10385E-05 | 3.2079E-05 |
| V/M | rs2050166133 |
None | 0.968 | N | 0.425 | 0.214 | 0.687798333245 | gnomAD-4.0.0 | 3.42767E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.50244E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.3404 | ambiguous | 0.4212 | ambiguous | -0.324 | Destabilizing | 0.78 | D | 0.415 | neutral | N | 0.482745367 | None | None | I |
| V/C | 0.7426 | likely_pathogenic | 0.8098 | pathogenic | -0.655 | Destabilizing | 0.999 | D | 0.537 | neutral | None | None | None | None | I |
| V/D | 0.6045 | likely_pathogenic | 0.7304 | pathogenic | -0.473 | Destabilizing | 0.996 | D | 0.645 | neutral | None | None | None | None | I |
| V/E | 0.4342 | ambiguous | 0.5146 | ambiguous | -0.593 | Destabilizing | 0.995 | D | 0.623 | neutral | N | 0.440031953 | None | None | I |
| V/F | 0.1688 | likely_benign | 0.2043 | benign | -0.687 | Destabilizing | 0.976 | D | 0.522 | neutral | None | None | None | None | I |
| V/G | 0.442 | ambiguous | 0.5563 | ambiguous | -0.404 | Destabilizing | 0.995 | D | 0.617 | neutral | N | 0.498677612 | None | None | I |
| V/H | 0.6317 | likely_pathogenic | 0.7121 | pathogenic | 0.013 | Stabilizing | 0.999 | D | 0.653 | neutral | None | None | None | None | I |
| V/I | 0.0668 | likely_benign | 0.0665 | benign | -0.259 | Destabilizing | 0.015 | N | 0.203 | neutral | None | None | None | None | I |
| V/K | 0.421 | ambiguous | 0.5067 | ambiguous | -0.407 | Destabilizing | 0.988 | D | 0.623 | neutral | None | None | None | None | I |
| V/L | 0.204 | likely_benign | 0.2304 | benign | -0.259 | Destabilizing | 0.011 | N | 0.19 | neutral | N | 0.457657708 | None | None | I |
| V/M | 0.1525 | likely_benign | 0.1602 | benign | -0.474 | Destabilizing | 0.968 | D | 0.425 | neutral | N | 0.513935066 | None | None | I |
| V/N | 0.3876 | ambiguous | 0.4854 | ambiguous | -0.156 | Destabilizing | 0.996 | D | 0.648 | neutral | None | None | None | None | I |
| V/P | 0.9462 | likely_pathogenic | 0.9712 | pathogenic | -0.251 | Destabilizing | 0.996 | D | 0.625 | neutral | None | None | None | None | I |
| V/Q | 0.3897 | ambiguous | 0.4561 | ambiguous | -0.399 | Destabilizing | 0.996 | D | 0.631 | neutral | None | None | None | None | I |
| V/R | 0.3992 | ambiguous | 0.4963 | ambiguous | 0.095 | Stabilizing | 0.996 | D | 0.649 | neutral | None | None | None | None | I |
| V/S | 0.34 | likely_benign | 0.4326 | ambiguous | -0.439 | Destabilizing | 0.988 | D | 0.572 | neutral | None | None | None | None | I |
| V/T | 0.3092 | likely_benign | 0.3716 | ambiguous | -0.468 | Destabilizing | 0.919 | D | 0.43 | neutral | None | None | None | None | I |
| V/W | 0.8329 | likely_pathogenic | 0.8731 | pathogenic | -0.76 | Destabilizing | 0.999 | D | 0.702 | prob.neutral | None | None | None | None | I |
| V/Y | 0.5457 | ambiguous | 0.6217 | pathogenic | -0.47 | Destabilizing | 0.996 | D | 0.515 | neutral | None | None | None | None | I |
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.