Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24681 | 74266;74267;74268 | chr2:178572091;178572090;178572089 | chr2:179436818;179436817;179436816 |
| N2AB | 23040 | 69343;69344;69345 | chr2:178572091;178572090;178572089 | chr2:179436818;179436817;179436816 |
| N2A | 22113 | 66562;66563;66564 | chr2:178572091;178572090;178572089 | chr2:179436818;179436817;179436816 |
| N2B | 15616 | 47071;47072;47073 | chr2:178572091;178572090;178572089 | chr2:179436818;179436817;179436816 |
| Novex-1 | 15741 | 47446;47447;47448 | chr2:178572091;178572090;178572089 | chr2:179436818;179436817;179436816 |
| Novex-2 | 15808 | 47647;47648;47649 | chr2:178572091;178572090;178572089 | chr2:179436818;179436817;179436816 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Q/R | rs537071956  |
0.108 | 0.201 | N | 0.459 | 0.178 | 0.203808441222 | gnomAD-2.1.1 | 4.08444E-04 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.12529E-03 | None | 4.90838E-04 | None | 0 | 0 | 0 |
| Q/R | rs537071956 |
0.108 | 0.201 | N | 0.459 | 0.178 | 0.203808441222 | gnomAD-3.1.2 | 1.77517E-04 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 4.84496E-03 | None | 0 | 0 | 1.47E-05 | 2.06954E-04 | 0 |
| Q/R | rs537071956 |
0.108 | 0.201 | N | 0.459 | 0.178 | 0.203808441222 | 1000 genomes | 9.98403E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 4E-03 | 0 | None | None | None | 1E-03 | None |
| Q/R | rs537071956 |
0.108 | 0.201 | N | 0.459 | 0.178 | 0.203808441222 | gnomAD-4.0.0 | 1.15295E-04 | None | None | None | None | N | None | 0 | 0 | None | 0 | 3.15606E-03 | None | 0 | 0 | 1.69558E-06 | 3.40472E-04 | 1.92141E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Q/A | 0.1556 | likely_benign | 0.1468 | benign | -0.358 | Destabilizing | 0.033 | N | 0.245 | neutral | None | None | None | None | N |
| Q/C | 0.7329 | likely_pathogenic | 0.7126 | pathogenic | 0.191 | Stabilizing | 0.984 | D | 0.482 | neutral | None | None | None | None | N |
| Q/D | 0.5676 | likely_pathogenic | 0.56 | ambiguous | -0.207 | Destabilizing | 0.434 | N | 0.434 | neutral | None | None | None | None | N |
| Q/E | 0.0803 | likely_benign | 0.0822 | benign | -0.213 | Destabilizing | 0.142 | N | 0.475 | neutral | N | 0.366944412 | None | None | N |
| Q/F | 0.8155 | likely_pathogenic | 0.7904 | pathogenic | -0.398 | Destabilizing | 0.969 | D | 0.516 | neutral | None | None | None | None | N |
| Q/G | 0.3675 | ambiguous | 0.3429 | ambiguous | -0.599 | Destabilizing | 0.719 | D | 0.419 | neutral | None | None | None | None | N |
| Q/H | 0.3074 | likely_benign | 0.2957 | benign | -0.544 | Destabilizing | 0.845 | D | 0.38 | neutral | N | 0.468052768 | None | None | N |
| Q/I | 0.4956 | ambiguous | 0.4817 | ambiguous | 0.204 | Stabilizing | 0.879 | D | 0.506 | neutral | None | None | None | None | N |
| Q/K | 0.1401 | likely_benign | 0.1358 | benign | -0.114 | Destabilizing | 0.002 | N | 0.195 | neutral | N | 0.450581728 | None | None | N |
| Q/L | 0.2198 | likely_benign | 0.2036 | benign | 0.204 | Stabilizing | 0.434 | N | 0.442 | neutral | N | 0.472727869 | None | None | N |
| Q/M | 0.3861 | ambiguous | 0.368 | ambiguous | 0.585 | Stabilizing | 0.957 | D | 0.381 | neutral | None | None | None | None | N |
| Q/N | 0.4228 | ambiguous | 0.4241 | ambiguous | -0.446 | Destabilizing | 0.434 | N | 0.422 | neutral | None | None | None | None | N |
| Q/P | 0.0934 | likely_benign | 0.0942 | benign | 0.047 | Stabilizing | 0.805 | D | 0.407 | neutral | N | 0.338821156 | None | None | N |
| Q/R | 0.1642 | likely_benign | 0.1518 | benign | 0.047 | Stabilizing | 0.201 | N | 0.459 | neutral | N | 0.478480406 | None | None | N |
| Q/S | 0.228 | likely_benign | 0.2288 | benign | -0.456 | Destabilizing | 0.561 | D | 0.388 | neutral | None | None | None | None | N |
| Q/T | 0.239 | likely_benign | 0.2337 | benign | -0.297 | Destabilizing | 0.09 | N | 0.4 | neutral | None | None | None | None | N |
| Q/V | 0.3179 | likely_benign | 0.301 | benign | 0.047 | Stabilizing | 0.234 | N | 0.473 | neutral | None | None | None | None | N |
| Q/W | 0.7744 | likely_pathogenic | 0.7396 | pathogenic | -0.327 | Destabilizing | 0.997 | D | 0.516 | neutral | None | None | None | None | N |
| Q/Y | 0.654 | likely_pathogenic | 0.6267 | pathogenic | -0.104 | Destabilizing | 0.969 | D | 0.405 | 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.