Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17315 | 52168;52169;52170 | chr2:178609367;178609366;178609365 | chr2:179474094;179474093;179474092 |
| N2AB | 15674 | 47245;47246;47247 | chr2:178609367;178609366;178609365 | chr2:179474094;179474093;179474092 |
| N2A | 14747 | 44464;44465;44466 | chr2:178609367;178609366;178609365 | chr2:179474094;179474093;179474092 |
| N2B | 8250 | 24973;24974;24975 | chr2:178609367;178609366;178609365 | chr2:179474094;179474093;179474092 |
| Novex-1 | 8375 | 25348;25349;25350 | chr2:178609367;178609366;178609365 | chr2:179474094;179474093;179474092 |
| Novex-2 | 8442 | 25549;25550;25551 | chr2:178609367;178609366;178609365 | chr2:179474094;179474093;179474092 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs1338519299  |
None | 0.003 | N | 0.245 | 0.044 | 0.282575091529 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/A | rs1338519299 |
None | 0.003 | N | 0.245 | 0.044 | 0.282575091529 | gnomAD-4.0.0 | 3.04559E-06 | None | None | None | None | N | None | 3.49638E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.40321E-05 |
| V/F | rs778099881 |
-0.636 | None | N | 0.189 | 0.114 | 0.128392430309 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| V/F | rs778099881 |
-0.636 | None | N | 0.189 | 0.114 | 0.128392430309 | gnomAD-4.0.0 | 1.36963E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.80003E-06 | 0 | 0 |
| V/I | rs778099881 |
-0.845 | None | N | 0.14 | 0.06 | 0.0954503805726 | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | N | None | 8.28E-05 | 2.83E-05 | None | 0 | 0 | None | 0 | None | 0 | 7.83E-06 | 0 |
| V/I | rs778099881 |
-0.845 | None | N | 0.14 | 0.06 | 0.0954503805726 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 4.42E-05 | 0 | 0 |
| V/I | rs778099881 |
-0.845 | None | N | 0.14 | 0.06 | 0.0954503805726 | gnomAD-4.0.0 | 8.68408E-06 | None | None | None | None | N | None | 5.34759E-05 | 1.66934E-05 | None | 0 | 0 | None | 0 | 1.6469E-04 | 6.78535E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.142 | likely_benign | 0.1557 | benign | -0.676 | Destabilizing | 0.003 | N | 0.245 | neutral | N | 0.469869283 | None | None | N |
| V/C | 0.3888 | ambiguous | 0.3898 | ambiguous | -0.729 | Destabilizing | 0.245 | N | 0.36 | neutral | None | None | None | None | N |
| V/D | 0.2022 | likely_benign | 0.1995 | benign | -0.425 | Destabilizing | 0.007 | N | 0.456 | neutral | N | 0.481779788 | None | None | N |
| V/E | 0.1819 | likely_benign | 0.1704 | benign | -0.447 | Destabilizing | 0.009 | N | 0.398 | neutral | None | None | None | None | N |
| V/F | 0.1103 | likely_benign | 0.1003 | benign | -0.594 | Destabilizing | None | N | 0.189 | neutral | N | 0.500538907 | None | None | N |
| V/G | 0.1768 | likely_benign | 0.186 | benign | -0.87 | Destabilizing | 0.007 | N | 0.438 | neutral | N | 0.470389358 | None | None | N |
| V/H | 0.2299 | likely_benign | 0.203 | benign | -0.195 | Destabilizing | None | N | 0.333 | neutral | None | None | None | None | N |
| V/I | 0.0762 | likely_benign | 0.0758 | benign | -0.265 | Destabilizing | None | N | 0.14 | neutral | N | 0.481433071 | None | None | N |
| V/K | 0.2224 | likely_benign | 0.2187 | benign | -0.543 | Destabilizing | 0.009 | N | 0.387 | neutral | None | None | None | None | N |
| V/L | 0.1288 | likely_benign | 0.1278 | benign | -0.265 | Destabilizing | 0.001 | N | 0.265 | neutral | N | 0.469869283 | None | None | N |
| V/M | 0.1565 | likely_benign | 0.1571 | benign | -0.6 | Destabilizing | 0.138 | N | 0.363 | neutral | None | None | None | None | N |
| V/N | 0.1522 | likely_benign | 0.1525 | benign | -0.51 | Destabilizing | 0.009 | N | 0.456 | neutral | None | None | None | None | N |
| V/P | 0.2439 | likely_benign | 0.2269 | benign | -0.371 | Destabilizing | 0.044 | N | 0.443 | neutral | None | None | None | None | N |
| V/Q | 0.1628 | likely_benign | 0.1555 | benign | -0.612 | Destabilizing | 0.001 | N | 0.303 | neutral | None | None | None | None | N |
| V/R | 0.1825 | likely_benign | 0.1737 | benign | -0.129 | Destabilizing | None | N | 0.357 | neutral | None | None | None | None | N |
| V/S | 0.1146 | likely_benign | 0.1306 | benign | -0.896 | Destabilizing | None | N | 0.247 | neutral | None | None | None | None | N |
| V/T | 0.1307 | likely_benign | 0.1449 | benign | -0.81 | Destabilizing | None | N | 0.096 | neutral | None | None | None | None | N |
| V/W | 0.5709 | likely_pathogenic | 0.5469 | ambiguous | -0.72 | Destabilizing | 0.245 | N | 0.442 | neutral | None | None | None | None | N |
| V/Y | 0.2554 | likely_benign | 0.2291 | benign | -0.422 | Destabilizing | 0.001 | N | 0.177 | 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.