Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29311 | 88156;88157;88158 | chr2:178557331;178557330;178557329 | chr2:179422058;179422057;179422056 |
| N2AB | 27670 | 83233;83234;83235 | chr2:178557331;178557330;178557329 | chr2:179422058;179422057;179422056 |
| N2A | 26743 | 80452;80453;80454 | chr2:178557331;178557330;178557329 | chr2:179422058;179422057;179422056 |
| N2B | 20246 | 60961;60962;60963 | chr2:178557331;178557330;178557329 | chr2:179422058;179422057;179422056 |
| Novex-1 | 20371 | 61336;61337;61338 | chr2:178557331;178557330;178557329 | chr2:179422058;179422057;179422056 |
| Novex-2 | 20438 | 61537;61538;61539 | chr2:178557331;178557330;178557329 | chr2:179422058;179422057;179422056 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/W | rs1245349093  |
-0.912 | 1.0 | D | 0.773 | 0.598 | 0.622057482502 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| R/W | rs1245349093 |
-0.912 | 1.0 | D | 0.773 | 0.598 | 0.622057482502 | gnomAD-4.0.0 | 1.591E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85773E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9748 | likely_pathogenic | 0.9723 | pathogenic | -2.285 | Highly Destabilizing | 0.931 | D | 0.567 | neutral | None | None | None | None | I |
| R/C | 0.6063 | likely_pathogenic | 0.5693 | pathogenic | -2.023 | Highly Destabilizing | 1.0 | D | 0.776 | deleterious | None | None | None | None | I |
| R/D | 0.9979 | likely_pathogenic | 0.998 | pathogenic | -1.578 | Destabilizing | 0.996 | D | 0.596 | neutral | None | None | None | None | I |
| R/E | 0.9682 | likely_pathogenic | 0.9688 | pathogenic | -1.344 | Destabilizing | 0.97 | D | 0.581 | neutral | None | None | None | None | I |
| R/F | 0.9857 | likely_pathogenic | 0.9819 | pathogenic | -1.272 | Destabilizing | 0.999 | D | 0.761 | deleterious | None | None | None | None | I |
| R/G | 0.9772 | likely_pathogenic | 0.9767 | pathogenic | -2.608 | Highly Destabilizing | 0.98 | D | 0.541 | neutral | D | 0.550034137 | None | None | I |
| R/H | 0.5022 | ambiguous | 0.4467 | ambiguous | -2.275 | Highly Destabilizing | 0.999 | D | 0.55 | neutral | None | None | None | None | I |
| R/I | 0.9264 | likely_pathogenic | 0.9116 | pathogenic | -1.317 | Destabilizing | 0.999 | D | 0.734 | prob.delet. | None | None | None | None | I |
| R/K | 0.3517 | ambiguous | 0.3332 | benign | -1.388 | Destabilizing | 0.122 | N | 0.252 | neutral | N | 0.48667879000000003 | None | None | I |
| R/L | 0.884 | likely_pathogenic | 0.8722 | pathogenic | -1.317 | Destabilizing | 0.985 | D | 0.541 | neutral | None | None | None | None | I |
| R/M | 0.9321 | likely_pathogenic | 0.9133 | pathogenic | -1.809 | Destabilizing | 1.0 | D | 0.644 | neutral | N | 0.516054126 | None | None | I |
| R/N | 0.9907 | likely_pathogenic | 0.9894 | pathogenic | -1.775 | Destabilizing | 0.985 | D | 0.547 | neutral | None | None | None | None | I |
| R/P | 0.9991 | likely_pathogenic | 0.9993 | pathogenic | -1.635 | Destabilizing | 0.999 | D | 0.636 | neutral | None | None | None | None | I |
| R/Q | 0.4723 | ambiguous | 0.4711 | ambiguous | -1.476 | Destabilizing | 0.97 | D | 0.604 | neutral | None | None | None | None | I |
| R/S | 0.9854 | likely_pathogenic | 0.9839 | pathogenic | -2.489 | Highly Destabilizing | 0.961 | D | 0.544 | neutral | D | 0.546738773 | None | None | I |
| R/T | 0.9635 | likely_pathogenic | 0.9577 | pathogenic | -2.05 | Highly Destabilizing | 0.98 | D | 0.523 | neutral | N | 0.505365703 | None | None | I |
| R/V | 0.9343 | likely_pathogenic | 0.9284 | pathogenic | -1.635 | Destabilizing | 0.996 | D | 0.657 | neutral | None | None | None | None | I |
| R/W | 0.8611 | likely_pathogenic | 0.8364 | pathogenic | -0.861 | Destabilizing | 1.0 | D | 0.773 | deleterious | D | 0.538931321 | None | None | I |
| R/Y | 0.9605 | likely_pathogenic | 0.9531 | pathogenic | -0.828 | Destabilizing | 0.999 | D | 0.705 | prob.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.