Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2405 | 7438;7439;7440 | chr2:178773955;178773954;178773953 | chr2:179638682;179638681;179638680 |
| N2AB | 2405 | 7438;7439;7440 | chr2:178773955;178773954;178773953 | chr2:179638682;179638681;179638680 |
| N2A | 2405 | 7438;7439;7440 | chr2:178773955;178773954;178773953 | chr2:179638682;179638681;179638680 |
| N2B | 2359 | 7300;7301;7302 | chr2:178773955;178773954;178773953 | chr2:179638682;179638681;179638680 |
| Novex-1 | 2359 | 7300;7301;7302 | chr2:178773955;178773954;178773953 | chr2:179638682;179638681;179638680 |
| Novex-2 | 2359 | 7300;7301;7302 | chr2:178773955;178773954;178773953 | chr2:179638682;179638681;179638680 |
| Novex-3 | 2405 | 7438;7439;7440 | chr2:178773955;178773954;178773953 | chr2:179638682;179638681;179638680 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | None | None | 0.982 | D | 0.692 | 0.39 | 0.456552270603 | gnomAD-4.0.0 | 1.59053E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85659E-06 | 0 | 0 |
| I/T | rs776126188  |
-0.526 | 0.991 | N | 0.671 | 0.587 | 0.686562002565 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.83E-06 | 0 |
| I/T | rs776126188 |
-0.526 | 0.991 | N | 0.671 | 0.587 | 0.686562002565 | gnomAD-4.0.0 | 4.10443E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.39581E-06 | 0 | 0 |
| I/V | rs1055161708 |
None | 0.58 | N | 0.355 | 0.109 | 0.530606565545 | gnomAD-4.0.0 | 1.36814E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99303E-07 | 1.15931E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.2195 | likely_benign | 0.1996 | benign | -1.04 | Destabilizing | 0.953 | D | 0.637 | neutral | None | None | None | None | N |
| I/C | 0.7252 | likely_pathogenic | 0.7102 | pathogenic | -0.571 | Destabilizing | 0.999 | D | 0.695 | prob.neutral | None | None | None | None | N |
| I/D | 0.7239 | likely_pathogenic | 0.7183 | pathogenic | -0.506 | Destabilizing | 0.998 | D | 0.769 | deleterious | None | None | None | None | N |
| I/E | 0.5199 | ambiguous | 0.5059 | ambiguous | -0.584 | Destabilizing | 0.998 | D | 0.77 | deleterious | None | None | None | None | N |
| I/F | 0.1902 | likely_benign | 0.1856 | benign | -0.969 | Destabilizing | 0.986 | D | 0.694 | prob.neutral | None | None | None | None | N |
| I/G | 0.6091 | likely_pathogenic | 0.5878 | pathogenic | -1.26 | Destabilizing | 0.998 | D | 0.767 | deleterious | None | None | None | None | N |
| I/H | 0.5124 | ambiguous | 0.4985 | ambiguous | -0.579 | Destabilizing | 0.999 | D | 0.757 | deleterious | None | None | None | None | N |
| I/K | 0.3152 | likely_benign | 0.2991 | benign | -0.562 | Destabilizing | 0.991 | D | 0.767 | deleterious | N | 0.473037016 | None | None | N |
| I/L | 0.1081 | likely_benign | 0.1053 | benign | -0.562 | Destabilizing | 0.02 | N | 0.283 | neutral | N | 0.493310231 | None | None | N |
| I/M | 0.0843 | likely_benign | 0.081 | benign | -0.368 | Destabilizing | 0.982 | D | 0.692 | prob.neutral | D | 0.548198286 | None | None | N |
| I/N | 0.3132 | likely_benign | 0.3049 | benign | -0.266 | Destabilizing | 0.998 | D | 0.774 | deleterious | None | None | None | None | N |
| I/P | 0.72 | likely_pathogenic | 0.7092 | pathogenic | -0.688 | Destabilizing | 0.998 | D | 0.776 | deleterious | None | None | None | None | N |
| I/Q | 0.3843 | ambiguous | 0.3679 | ambiguous | -0.523 | Destabilizing | 0.998 | D | 0.767 | deleterious | None | None | None | None | N |
| I/R | 0.2402 | likely_benign | 0.2307 | benign | 0.037 | Stabilizing | 0.991 | D | 0.777 | deleterious | N | 0.489558064 | None | None | N |
| I/S | 0.255 | likely_benign | 0.2439 | benign | -0.764 | Destabilizing | 0.993 | D | 0.723 | prob.delet. | None | None | None | None | N |
| I/T | 0.1025 | likely_benign | 0.0962 | benign | -0.732 | Destabilizing | 0.991 | D | 0.671 | neutral | N | 0.498560541 | None | None | N |
| I/V | 0.0859 | likely_benign | 0.0842 | benign | -0.688 | Destabilizing | 0.58 | D | 0.355 | neutral | N | 0.487432476 | None | None | N |
| I/W | 0.6997 | likely_pathogenic | 0.6937 | pathogenic | -0.987 | Destabilizing | 0.999 | D | 0.734 | prob.delet. | None | None | None | None | N |
| I/Y | 0.5834 | likely_pathogenic | 0.5812 | pathogenic | -0.741 | Destabilizing | 0.993 | D | 0.695 | prob.neutral | None | None | 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.