Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18022 | 54289;54290;54291 | chr2:178605113;178605112;178605111 | chr2:179469840;179469839;179469838 |
| N2AB | 16381 | 49366;49367;49368 | chr2:178605113;178605112;178605111 | chr2:179469840;179469839;179469838 |
| N2A | 15454 | 46585;46586;46587 | chr2:178605113;178605112;178605111 | chr2:179469840;179469839;179469838 |
| N2B | 8957 | 27094;27095;27096 | chr2:178605113;178605112;178605111 | chr2:179469840;179469839;179469838 |
| Novex-1 | 9082 | 27469;27470;27471 | chr2:178605113;178605112;178605111 | chr2:179469840;179469839;179469838 |
| Novex-2 | 9149 | 27670;27671;27672 | chr2:178605113;178605112;178605111 | chr2:179469840;179469839;179469838 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/C | None | None | 0.999 | N | 0.552 | 0.202 | 0.242244723065 | gnomAD-4.0.0 | 3.60097E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.93751E-06 | 0 | 0 |
| S/F | None | None | 0.996 | N | 0.585 | 0.238 | 0.188950314367 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.66327E-05 |
| S/P | rs188437486  |
-0.121 | 0.996 | N | 0.605 | 0.204 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.9478E-04 | None | 0 | 0 | 0 | 0 | 0 |
| S/P | rs188437486 |
-0.121 | 0.996 | N | 0.605 | 0.204 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| S/P | rs188437486 |
-0.121 | 0.996 | N | 0.605 | 0.204 | None | gnomAD-4.0.0 | 6.5773E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.95236E-04 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1911 | likely_benign | 0.1641 | benign | -0.263 | Destabilizing | 0.826 | D | 0.398 | neutral | N | 0.435851844 | None | None | N |
| S/C | 0.2275 | likely_benign | 0.2467 | benign | -0.251 | Destabilizing | 0.999 | D | 0.552 | neutral | N | 0.47485295 | None | None | N |
| S/D | 0.5625 | ambiguous | 0.5822 | pathogenic | 0.066 | Stabilizing | 0.046 | N | 0.255 | neutral | None | None | None | None | N |
| S/E | 0.8354 | likely_pathogenic | 0.8132 | pathogenic | -0.03 | Destabilizing | 0.884 | D | 0.529 | neutral | None | None | None | None | N |
| S/F | 0.5656 | likely_pathogenic | 0.5098 | ambiguous | -0.831 | Destabilizing | 0.996 | D | 0.585 | neutral | N | 0.473986158 | None | None | N |
| S/G | 0.1184 | likely_benign | 0.1239 | benign | -0.374 | Destabilizing | 0.007 | N | 0.207 | neutral | None | None | None | None | N |
| S/H | 0.596 | likely_pathogenic | 0.5874 | pathogenic | -0.775 | Destabilizing | 0.999 | D | 0.57 | neutral | None | None | None | None | N |
| S/I | 0.5576 | ambiguous | 0.4795 | ambiguous | -0.104 | Destabilizing | 0.997 | D | 0.608 | neutral | None | None | None | None | N |
| S/K | 0.917 | likely_pathogenic | 0.9086 | pathogenic | -0.48 | Destabilizing | 0.939 | D | 0.569 | neutral | None | None | None | None | N |
| S/L | 0.2608 | likely_benign | 0.2182 | benign | -0.104 | Destabilizing | 0.969 | D | 0.577 | neutral | None | None | None | None | N |
| S/M | 0.4313 | ambiguous | 0.3809 | ambiguous | 0.059 | Stabilizing | 0.999 | D | 0.553 | neutral | None | None | None | None | N |
| S/N | 0.1903 | likely_benign | 0.2082 | benign | -0.181 | Destabilizing | 0.939 | D | 0.534 | neutral | None | None | None | None | N |
| S/P | 0.9099 | likely_pathogenic | 0.8611 | pathogenic | -0.128 | Destabilizing | 0.996 | D | 0.605 | neutral | N | 0.474159516 | None | None | N |
| S/Q | 0.8051 | likely_pathogenic | 0.7846 | pathogenic | -0.436 | Destabilizing | 0.991 | D | 0.615 | neutral | None | None | None | None | N |
| S/R | 0.893 | likely_pathogenic | 0.8844 | pathogenic | -0.202 | Destabilizing | 0.991 | D | 0.601 | neutral | None | None | None | None | N |
| S/T | 0.1086 | likely_benign | 0.1047 | benign | -0.29 | Destabilizing | 0.959 | D | 0.523 | neutral | N | 0.454610963 | None | None | N |
| S/V | 0.512 | ambiguous | 0.4455 | ambiguous | -0.128 | Destabilizing | 0.997 | D | 0.593 | neutral | None | None | None | None | N |
| S/W | 0.7033 | likely_pathogenic | 0.6758 | pathogenic | -0.86 | Destabilizing | 0.999 | D | 0.633 | neutral | None | None | None | None | N |
| S/Y | 0.5185 | ambiguous | 0.482 | ambiguous | -0.576 | Destabilizing | 0.996 | D | 0.586 | neutral | N | 0.473986158 | 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.