Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20729 | 62410;62411;62412 | chr2:178589540;178589539;178589538 | chr2:179454267;179454266;179454265 |
| N2AB | 19088 | 57487;57488;57489 | chr2:178589540;178589539;178589538 | chr2:179454267;179454266;179454265 |
| N2A | 18161 | 54706;54707;54708 | chr2:178589540;178589539;178589538 | chr2:179454267;179454266;179454265 |
| N2B | 11664 | 35215;35216;35217 | chr2:178589540;178589539;178589538 | chr2:179454267;179454266;179454265 |
| Novex-1 | 11789 | 35590;35591;35592 | chr2:178589540;178589539;178589538 | chr2:179454267;179454266;179454265 |
| Novex-2 | 11856 | 35791;35792;35793 | chr2:178589540;178589539;178589538 | chr2:179454267;179454266;179454265 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | None | None | 0.003 | N | 0.193 | 0.173 | 0.554640639675 | gnomAD-4.0.0 | 1.59214E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02535E-05 |
| M/V | None | None | 0.021 | N | 0.297 | 0.164 | 0.525767821325 | gnomAD-4.0.0 | 1.59209E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85917E-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 | 0.6309 | likely_pathogenic | 0.666 | pathogenic | -1.924 | Destabilizing | 0.228 | N | 0.354 | neutral | None | None | None | None | N |
| M/C | 0.84 | likely_pathogenic | 0.8276 | pathogenic | -1.191 | Destabilizing | 0.94 | D | 0.514 | neutral | None | None | None | None | N |
| M/D | 0.9693 | likely_pathogenic | 0.9701 | pathogenic | -0.582 | Destabilizing | 0.94 | D | 0.592 | neutral | None | None | None | None | N |
| M/E | 0.7825 | likely_pathogenic | 0.7603 | pathogenic | -0.456 | Destabilizing | 0.593 | D | 0.565 | neutral | None | None | None | None | N |
| M/F | 0.6124 | likely_pathogenic | 0.6989 | pathogenic | -0.658 | Destabilizing | 0.264 | N | 0.386 | neutral | None | None | None | None | N |
| M/G | 0.911 | likely_pathogenic | 0.9233 | pathogenic | -2.307 | Highly Destabilizing | 0.593 | D | 0.525 | neutral | None | None | None | None | N |
| M/H | 0.7768 | likely_pathogenic | 0.7821 | pathogenic | -1.318 | Destabilizing | 0.94 | D | 0.514 | neutral | None | None | None | None | N |
| M/I | 0.5457 | ambiguous | 0.6734 | pathogenic | -0.878 | Destabilizing | 0.003 | N | 0.193 | neutral | N | 0.449869652 | None | None | N |
| M/K | 0.3532 | ambiguous | 0.3633 | ambiguous | -0.683 | Destabilizing | 0.523 | D | 0.472 | neutral | N | 0.419893462 | None | None | N |
| M/L | 0.1553 | likely_benign | 0.208 | benign | -0.878 | Destabilizing | None | N | 0.163 | neutral | N | 0.404521365 | None | None | N |
| M/N | 0.8288 | likely_pathogenic | 0.8529 | pathogenic | -0.772 | Destabilizing | 0.94 | D | 0.619 | neutral | None | None | None | None | N |
| M/P | 0.9188 | likely_pathogenic | 0.9159 | pathogenic | -1.204 | Destabilizing | 0.94 | D | 0.62 | neutral | None | None | None | None | N |
| M/Q | 0.4354 | ambiguous | 0.3527 | ambiguous | -0.674 | Destabilizing | 0.94 | D | 0.492 | neutral | None | None | None | None | N |
| M/R | 0.4248 | ambiguous | 0.4163 | ambiguous | -0.386 | Destabilizing | 0.523 | D | 0.583 | neutral | N | 0.407657671 | None | None | N |
| M/S | 0.7562 | likely_pathogenic | 0.7563 | pathogenic | -1.446 | Destabilizing | 0.593 | D | 0.442 | neutral | None | None | None | None | N |
| M/T | 0.4553 | ambiguous | 0.5079 | ambiguous | -1.197 | Destabilizing | 0.183 | N | 0.419 | neutral | N | 0.368613706 | None | None | N |
| M/V | 0.1381 | likely_benign | 0.1882 | benign | -1.204 | Destabilizing | 0.021 | N | 0.297 | neutral | N | 0.438479223 | None | None | N |
| M/W | 0.8487 | likely_pathogenic | 0.9095 | pathogenic | -0.687 | Destabilizing | 0.983 | D | 0.498 | neutral | None | None | None | None | N |
| M/Y | 0.8002 | likely_pathogenic | 0.8483 | pathogenic | -0.711 | Destabilizing | 0.836 | D | 0.593 | 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.