Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31359 | 94300;94301;94302 | chr2:178547551;178547550;178547549 | chr2:179412278;179412277;179412276 |
| N2AB | 29718 | 89377;89378;89379 | chr2:178547551;178547550;178547549 | chr2:179412278;179412277;179412276 |
| N2A | 28791 | 86596;86597;86598 | chr2:178547551;178547550;178547549 | chr2:179412278;179412277;179412276 |
| N2B | 22294 | 67105;67106;67107 | chr2:178547551;178547550;178547549 | chr2:179412278;179412277;179412276 |
| Novex-1 | 22419 | 67480;67481;67482 | chr2:178547551;178547550;178547549 | chr2:179412278;179412277;179412276 |
| Novex-2 | 22486 | 67681;67682;67683 | chr2:178547551;178547550;178547549 | chr2:179412278;179412277;179412276 |
| 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/I | rs780436747  |
-0.081 | 0.002 | N | 0.223 | 0.106 | 0.233150807113 | gnomAD-2.1.1 | 3.57E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 7.04E-05 | 1.40489E-04 |
| V/I | rs780436747 |
-0.081 | 0.002 | N | 0.223 | 0.106 | 0.233150807113 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 2.07125E-04 | 0 |
| V/I | rs780436747 |
-0.081 | 0.002 | N | 0.223 | 0.106 | 0.233150807113 | gnomAD-4.0.0 | 5.20561E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.03509E-05 | 1.09786E-05 | 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 | 0.773 | likely_pathogenic | 0.6856 | pathogenic | -1.38 | Destabilizing | 0.334 | N | 0.424 | neutral | N | 0.471293106 | None | None | I |
| V/C | 0.8866 | likely_pathogenic | 0.8657 | pathogenic | -1.042 | Destabilizing | 0.982 | D | 0.666 | neutral | None | None | None | None | I |
| V/D | 0.9899 | likely_pathogenic | 0.9819 | pathogenic | -1.165 | Destabilizing | 0.781 | D | 0.755 | deleterious | D | 0.525049666 | None | None | I |
| V/E | 0.9625 | likely_pathogenic | 0.9357 | pathogenic | -1.129 | Destabilizing | 0.826 | D | 0.714 | prob.delet. | None | None | None | None | I |
| V/F | 0.7019 | likely_pathogenic | 0.652 | pathogenic | -0.959 | Destabilizing | 0.638 | D | 0.696 | prob.neutral | N | 0.480381232 | None | None | I |
| V/G | 0.9282 | likely_pathogenic | 0.8889 | pathogenic | -1.727 | Destabilizing | 0.781 | D | 0.759 | deleterious | N | 0.507198901 | None | None | I |
| V/H | 0.9832 | likely_pathogenic | 0.9726 | pathogenic | -1.194 | Destabilizing | 0.982 | D | 0.715 | prob.delet. | None | None | None | None | I |
| V/I | 0.0669 | likely_benign | 0.0721 | benign | -0.519 | Destabilizing | 0.002 | N | 0.223 | neutral | N | 0.484232942 | None | None | I |
| V/K | 0.9759 | likely_pathogenic | 0.9599 | pathogenic | -1.266 | Destabilizing | 0.826 | D | 0.719 | prob.delet. | None | None | None | None | I |
| V/L | 0.3927 | ambiguous | 0.3566 | ambiguous | -0.519 | Destabilizing | 0.034 | N | 0.366 | neutral | N | 0.519980312 | None | None | I |
| V/M | 0.4792 | ambiguous | 0.4538 | ambiguous | -0.471 | Destabilizing | 0.7 | D | 0.634 | neutral | None | None | None | None | I |
| V/N | 0.9592 | likely_pathogenic | 0.936 | pathogenic | -1.201 | Destabilizing | 0.935 | D | 0.751 | deleterious | None | None | None | None | I |
| V/P | 0.9858 | likely_pathogenic | 0.9798 | pathogenic | -0.771 | Destabilizing | 0.935 | D | 0.724 | prob.delet. | None | None | None | None | I |
| V/Q | 0.9468 | likely_pathogenic | 0.9106 | pathogenic | -1.285 | Destabilizing | 0.935 | D | 0.713 | prob.delet. | None | None | None | None | I |
| V/R | 0.9594 | likely_pathogenic | 0.9338 | pathogenic | -0.794 | Destabilizing | 0.826 | D | 0.748 | deleterious | None | None | None | None | I |
| V/S | 0.9056 | likely_pathogenic | 0.8608 | pathogenic | -1.741 | Destabilizing | 0.826 | D | 0.728 | prob.delet. | None | None | None | None | I |
| V/T | 0.8074 | likely_pathogenic | 0.7492 | pathogenic | -1.581 | Destabilizing | 0.399 | N | 0.551 | neutral | None | None | None | None | I |
| V/W | 0.9866 | likely_pathogenic | 0.9813 | pathogenic | -1.194 | Destabilizing | 0.982 | D | 0.735 | prob.delet. | None | None | None | None | I |
| V/Y | 0.9566 | likely_pathogenic | 0.9418 | pathogenic | -0.871 | Destabilizing | 0.826 | D | 0.701 | prob.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.