Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 955 | 3088;3089;3090 | chr2:178783043;178783042;178783041 | chr2:179647770;179647769;179647768 |
| N2AB | 955 | 3088;3089;3090 | chr2:178783043;178783042;178783041 | chr2:179647770;179647769;179647768 |
| N2A | 955 | 3088;3089;3090 | chr2:178783043;178783042;178783041 | chr2:179647770;179647769;179647768 |
| N2B | 909 | 2950;2951;2952 | chr2:178783043;178783042;178783041 | chr2:179647770;179647769;179647768 |
| Novex-1 | 909 | 2950;2951;2952 | chr2:178783043;178783042;178783041 | chr2:179647770;179647769;179647768 |
| Novex-2 | 909 | 2950;2951;2952 | chr2:178783043;178783042;178783041 | chr2:179647770;179647769;179647768 |
| Novex-3 | 955 | 3088;3089;3090 | chr2:178783043;178783042;178783041 | chr2:179647770;179647769;179647768 |
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/L | rs762556628  |
-0.01 | 0.007 | N | 0.213 | 0.06 | 0.346315397577 | gnomAD-2.1.1 | 4E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.83E-06 | 0 |
| I/V | rs762556628 |
-0.079 | None | N | 0.159 | 0.079 | 0.422883881359 | gnomAD-2.1.1 | 4E-06 | None | None | None | None | I | None | 6.38E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs762556628 |
-0.079 | None | N | 0.159 | 0.079 | 0.422883881359 | gnomAD-4.0.0 | 4.80134E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.25007E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3023 | likely_benign | 0.3251 | benign | -1.032 | Destabilizing | 0.061 | N | 0.293 | neutral | None | None | None | None | I |
| I/C | 0.8774 | likely_pathogenic | 0.8771 | pathogenic | -0.811 | Destabilizing | 0.94 | D | 0.401 | neutral | None | None | None | None | I |
| I/D | 0.84 | likely_pathogenic | 0.8647 | pathogenic | -0.594 | Destabilizing | 0.418 | N | 0.487 | neutral | None | None | None | None | I |
| I/E | 0.6224 | likely_pathogenic | 0.6736 | pathogenic | -0.664 | Destabilizing | 0.418 | N | 0.485 | neutral | None | None | None | None | I |
| I/F | 0.2813 | likely_benign | 0.3127 | benign | -0.819 | Destabilizing | 0.002 | N | 0.201 | neutral | None | None | None | None | I |
| I/G | 0.7816 | likely_pathogenic | 0.8045 | pathogenic | -1.239 | Destabilizing | 0.418 | N | 0.477 | neutral | None | None | None | None | I |
| I/H | 0.6491 | likely_pathogenic | 0.6893 | pathogenic | -0.379 | Destabilizing | 0.94 | D | 0.453 | neutral | None | None | None | None | I |
| I/K | 0.3418 | ambiguous | 0.4066 | ambiguous | -0.726 | Destabilizing | 0.351 | N | 0.494 | neutral | N | 0.427084668 | None | None | I |
| I/L | 0.1678 | likely_benign | 0.1714 | benign | -0.587 | Destabilizing | 0.007 | N | 0.213 | neutral | N | 0.439474788 | None | None | I |
| I/M | 0.1157 | likely_benign | 0.1216 | benign | -0.561 | Destabilizing | 0.003 | N | 0.187 | neutral | N | 0.446903547 | None | None | I |
| I/N | 0.4349 | ambiguous | 0.4812 | ambiguous | -0.573 | Destabilizing | 0.418 | N | 0.492 | neutral | None | None | None | None | I |
| I/P | 0.8332 | likely_pathogenic | 0.8539 | pathogenic | -0.702 | Destabilizing | 0.593 | D | 0.48 | neutral | None | None | None | None | I |
| I/Q | 0.463 | ambiguous | 0.5142 | ambiguous | -0.818 | Destabilizing | 0.836 | D | 0.485 | neutral | None | None | None | None | I |
| I/R | 0.2557 | likely_benign | 0.3126 | benign | -0.063 | Destabilizing | 0.351 | N | 0.474 | neutral | N | 0.449148974 | None | None | I |
| I/S | 0.3563 | ambiguous | 0.3931 | ambiguous | -1.047 | Destabilizing | 0.129 | N | 0.47 | neutral | None | None | None | None | I |
| I/T | 0.1061 | likely_benign | 0.1164 | benign | -1.012 | Destabilizing | 0.001 | N | 0.22 | neutral | N | 0.455502248 | None | None | I |
| I/V | 0.084 | likely_benign | 0.082 | benign | -0.702 | Destabilizing | None | N | 0.159 | neutral | N | 0.400603106 | None | None | I |
| I/W | 0.8637 | likely_pathogenic | 0.8731 | pathogenic | -0.813 | Destabilizing | 0.983 | D | 0.446 | neutral | None | None | None | None | I |
| I/Y | 0.7189 | likely_pathogenic | 0.7503 | pathogenic | -0.604 | Destabilizing | 0.264 | N | 0.451 | 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.