Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2094 | 6505;6506;6507 | chr2:178775584;178775583;178775582 | chr2:179640311;179640310;179640309 |
| N2AB | 2094 | 6505;6506;6507 | chr2:178775584;178775583;178775582 | chr2:179640311;179640310;179640309 |
| N2A | 2094 | 6505;6506;6507 | chr2:178775584;178775583;178775582 | chr2:179640311;179640310;179640309 |
| N2B | 2048 | 6367;6368;6369 | chr2:178775584;178775583;178775582 | chr2:179640311;179640310;179640309 |
| Novex-1 | 2048 | 6367;6368;6369 | chr2:178775584;178775583;178775582 | chr2:179640311;179640310;179640309 |
| Novex-2 | 2048 | 6367;6368;6369 | chr2:178775584;178775583;178775582 | chr2:179640311;179640310;179640309 |
| Novex-3 | 2094 | 6505;6506;6507 | chr2:178775584;178775583;178775582 | chr2:179640311;179640310;179640309 |
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 | 0.02 | N | 0.21 | 0.181 | 0.283761946502 | gnomAD-4.0.0 | 1.59066E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 2.4108E-04 | 0 | 0 | 0 |
| D/H | None | None | 0.998 | D | 0.597 | 0.552 | 0.454426139905 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-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 | 0.4899 | ambiguous | 0.4642 | ambiguous | -0.477 | Destabilizing | 0.939 | D | 0.491 | neutral | N | 0.506712461 | None | None | N |
| D/C | 0.9519 | likely_pathogenic | 0.943 | pathogenic | -0.199 | Destabilizing | 0.999 | D | 0.742 | deleterious | None | None | None | None | N |
| D/E | 0.3378 | likely_benign | 0.3011 | benign | -0.718 | Destabilizing | 0.02 | N | 0.21 | neutral | N | 0.467666588 | None | None | N |
| D/F | 0.9221 | likely_pathogenic | 0.9069 | pathogenic | -0.285 | Destabilizing | 0.998 | D | 0.736 | prob.delet. | None | None | None | None | N |
| D/G | 0.663 | likely_pathogenic | 0.6338 | pathogenic | -0.786 | Destabilizing | 0.969 | D | 0.476 | neutral | D | 0.556999715 | None | None | N |
| D/H | 0.755 | likely_pathogenic | 0.6989 | pathogenic | -0.606 | Destabilizing | 0.998 | D | 0.597 | neutral | D | 0.547965631 | None | None | N |
| D/I | 0.8052 | likely_pathogenic | 0.7527 | pathogenic | 0.322 | Stabilizing | 0.993 | D | 0.739 | prob.delet. | None | None | None | None | N |
| D/K | 0.8547 | likely_pathogenic | 0.8086 | pathogenic | -0.467 | Destabilizing | 0.91 | D | 0.434 | neutral | None | None | None | None | N |
| D/L | 0.8086 | likely_pathogenic | 0.7829 | pathogenic | 0.322 | Stabilizing | 0.986 | D | 0.719 | prob.delet. | None | None | None | None | N |
| D/M | 0.9177 | likely_pathogenic | 0.8978 | pathogenic | 0.724 | Stabilizing | 0.999 | D | 0.723 | prob.delet. | None | None | None | None | N |
| D/N | 0.2374 | likely_benign | 0.2051 | benign | -0.767 | Destabilizing | 0.939 | D | 0.462 | neutral | N | 0.510675662 | None | None | N |
| D/P | 0.9159 | likely_pathogenic | 0.9041 | pathogenic | 0.081 | Stabilizing | 0.993 | D | 0.586 | neutral | None | None | None | None | N |
| D/Q | 0.7948 | likely_pathogenic | 0.7482 | pathogenic | -0.654 | Destabilizing | 0.973 | D | 0.466 | neutral | None | None | None | None | N |
| D/R | 0.8826 | likely_pathogenic | 0.8487 | pathogenic | -0.306 | Destabilizing | 0.986 | D | 0.681 | prob.neutral | None | None | None | None | N |
| D/S | 0.3274 | likely_benign | 0.2897 | benign | -0.967 | Destabilizing | 0.953 | D | 0.399 | neutral | None | None | None | None | N |
| D/T | 0.5634 | ambiguous | 0.5091 | ambiguous | -0.729 | Destabilizing | 0.986 | D | 0.509 | neutral | None | None | None | None | N |
| D/V | 0.5879 | likely_pathogenic | 0.5334 | ambiguous | 0.081 | Stabilizing | 0.991 | D | 0.71 | prob.delet. | N | 0.511094506 | None | None | N |
| D/W | 0.9886 | likely_pathogenic | 0.9849 | pathogenic | -0.182 | Destabilizing | 0.999 | D | 0.736 | prob.delet. | None | None | None | None | N |
| D/Y | 0.7004 | likely_pathogenic | 0.6521 | pathogenic | -0.09 | Destabilizing | 0.997 | D | 0.735 | prob.delet. | D | 0.583563682 | 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.