Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3121 | 9586;9587;9588 | chr2:178767869;178767868;178767867 | chr2:179632596;179632595;179632594 |
| N2AB | 3121 | 9586;9587;9588 | chr2:178767869;178767868;178767867 | chr2:179632596;179632595;179632594 |
| N2A | 3121 | 9586;9587;9588 | chr2:178767869;178767868;178767867 | chr2:179632596;179632595;179632594 |
| N2B | 3075 | 9448;9449;9450 | chr2:178767869;178767868;178767867 | chr2:179632596;179632595;179632594 |
| Novex-1 | 3075 | 9448;9449;9450 | chr2:178767869;178767868;178767867 | chr2:179632596;179632595;179632594 |
| Novex-2 | 3075 | 9448;9449;9450 | chr2:178767869;178767868;178767867 | chr2:179632596;179632595;179632594 |
| Novex-3 | 3121 | 9586;9587;9588 | chr2:178767869;178767868;178767867 | chr2:179632596;179632595;179632594 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | rs200413367  |
0.365 | 0.828 | N | 0.387 | 0.206 | 0.287603790349 | gnomAD-2.1.1 | 7.57E-05 | None | None | None | None | I | None | 0 | 0 | None | 1.1919E-03 | 0 | None | 0 | None | 0 | 4.41E-05 | 3.26584E-04 |
| M/I | rs200413367 |
0.365 | 0.828 | N | 0.387 | 0.206 | 0.287603790349 | gnomAD-3.1.2 | 6.57E-05 | None | None | None | None | I | None | 0 | 6.55E-05 | 0 | 2.01729E-03 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| M/I | rs200413367 |
0.365 | 0.828 | N | 0.387 | 0.206 | 0.287603790349 | gnomAD-4.0.0 | 4.58483E-05 | None | None | None | None | I | None | 0 | 1.66672E-05 | None | 1.51996E-03 | 0 | None | 0 | 0 | 1.61016E-05 | 0 | 1.44032E-04 |
| M/V | None | None | 0.828 | N | 0.395 | 0.177 | 0.258779203287 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.8023 | likely_pathogenic | 0.7881 | pathogenic | -0.452 | Destabilizing | 0.963 | D | 0.36 | neutral | None | None | None | None | I |
| M/C | 0.9575 | likely_pathogenic | 0.9547 | pathogenic | -0.516 | Destabilizing | 1.0 | D | 0.297 | neutral | None | None | None | None | I |
| M/D | 0.9668 | likely_pathogenic | 0.9653 | pathogenic | 0.446 | Stabilizing | 0.999 | D | 0.377 | neutral | None | None | None | None | I |
| M/E | 0.8621 | likely_pathogenic | 0.8369 | pathogenic | 0.394 | Stabilizing | 0.999 | D | 0.356 | neutral | None | None | None | None | I |
| M/F | 0.4766 | ambiguous | 0.4779 | ambiguous | -0.111 | Destabilizing | 0.969 | D | 0.301 | neutral | None | None | None | None | I |
| M/G | 0.9159 | likely_pathogenic | 0.9153 | pathogenic | -0.635 | Destabilizing | 0.999 | D | 0.371 | neutral | None | None | None | None | I |
| M/H | 0.8452 | likely_pathogenic | 0.845 | pathogenic | 0.174 | Stabilizing | 1.0 | D | 0.357 | neutral | None | None | None | None | I |
| M/I | 0.5676 | likely_pathogenic | 0.614 | pathogenic | -0.068 | Destabilizing | 0.828 | D | 0.387 | neutral | N | 0.341049859 | None | None | I |
| M/K | 0.5655 | likely_pathogenic | 0.5652 | pathogenic | 0.526 | Stabilizing | 0.993 | D | 0.342 | neutral | N | 0.343295863 | None | None | I |
| M/L | 0.151 | likely_benign | 0.1444 | benign | -0.068 | Destabilizing | 0.03 | N | 0.166 | neutral | N | 0.332575702 | None | None | I |
| M/N | 0.817 | likely_pathogenic | 0.8139 | pathogenic | 0.653 | Stabilizing | 0.999 | D | 0.371 | neutral | None | None | None | None | I |
| M/P | 0.8482 | likely_pathogenic | 0.8535 | pathogenic | -0.166 | Destabilizing | 0.999 | D | 0.374 | neutral | None | None | None | None | I |
| M/Q | 0.5829 | likely_pathogenic | 0.559 | ambiguous | 0.48 | Stabilizing | 0.999 | D | 0.285 | neutral | None | None | None | None | I |
| M/R | 0.5951 | likely_pathogenic | 0.6044 | pathogenic | 0.979 | Stabilizing | 0.998 | D | 0.304 | neutral | N | 0.348049521 | None | None | I |
| M/S | 0.819 | likely_pathogenic | 0.8144 | pathogenic | 0.154 | Stabilizing | 0.995 | D | 0.355 | neutral | None | None | None | None | I |
| M/T | 0.7365 | likely_pathogenic | 0.7261 | pathogenic | 0.208 | Stabilizing | 0.979 | D | 0.332 | neutral | N | 0.347301391 | None | None | I |
| M/V | 0.2079 | likely_benign | 0.224 | benign | -0.166 | Destabilizing | 0.828 | D | 0.395 | neutral | N | 0.345627826 | None | None | I |
| M/W | 0.8409 | likely_pathogenic | 0.8494 | pathogenic | -0.077 | Destabilizing | 1.0 | D | 0.34 | neutral | None | None | None | None | I |
| M/Y | 0.7623 | likely_pathogenic | 0.764 | pathogenic | 0.094 | Stabilizing | 0.999 | D | 0.303 | 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.