Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30013 | 90262;90263;90264 | chr2:178552863;178552862;178552861 | chr2:179417590;179417589;179417588 |
| N2AB | 28372 | 85339;85340;85341 | chr2:178552863;178552862;178552861 | chr2:179417590;179417589;179417588 |
| N2A | 27445 | 82558;82559;82560 | chr2:178552863;178552862;178552861 | chr2:179417590;179417589;179417588 |
| N2B | 20948 | 63067;63068;63069 | chr2:178552863;178552862;178552861 | chr2:179417590;179417589;179417588 |
| Novex-1 | 21073 | 63442;63443;63444 | chr2:178552863;178552862;178552861 | chr2:179417590;179417589;179417588 |
| Novex-2 | 21140 | 63643;63644;63645 | chr2:178552863;178552862;178552861 | chr2:179417590;179417589;179417588 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs369899112  |
-0.121 | 0.014 | N | 0.399 | 0.073 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| I/T | rs369899112 |
-0.121 | 0.014 | N | 0.399 | 0.073 | None | gnomAD-4.0.0 | 1.59128E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43279E-05 | 0 |
| I/V | rs902222433 |
-0.044 | None | N | 0.127 | 0.091 | 0.229264304666 | gnomAD-2.1.1 | 7.15E-06 | None | None | None | None | I | None | 8.27E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs902222433 |
-0.044 | None | N | 0.127 | 0.091 | 0.229264304666 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 4.82E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs902222433 |
-0.044 | None | N | 0.127 | 0.091 | 0.229264304666 | gnomAD-4.0.0 | 3.04478E-06 | None | None | None | None | I | None | 3.49345E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 4.69704E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.2549 | likely_benign | 0.1998 | benign | -0.539 | Destabilizing | 0.004 | N | 0.334 | neutral | None | None | None | None | I |
| I/C | 0.5198 | ambiguous | 0.4644 | ambiguous | -0.673 | Destabilizing | 0.497 | N | 0.455 | neutral | None | None | None | None | I |
| I/D | 0.6923 | likely_pathogenic | 0.605 | pathogenic | -0.168 | Destabilizing | 0.022 | N | 0.496 | neutral | None | None | None | None | I |
| I/E | 0.6187 | likely_pathogenic | 0.5381 | ambiguous | -0.276 | Destabilizing | 0.018 | N | 0.496 | neutral | None | None | None | None | I |
| I/F | 0.0944 | likely_benign | 0.0874 | benign | -0.653 | Destabilizing | None | N | 0.128 | neutral | N | 0.383012729 | None | None | I |
| I/G | 0.6517 | likely_pathogenic | 0.5604 | ambiguous | -0.666 | Destabilizing | 0.009 | N | 0.498 | neutral | None | None | None | None | I |
| I/H | 0.3403 | ambiguous | 0.2983 | benign | 0.037 | Stabilizing | None | N | 0.301 | neutral | None | None | None | None | I |
| I/K | 0.4465 | ambiguous | 0.3929 | ambiguous | -0.243 | Destabilizing | 0.009 | N | 0.487 | neutral | None | None | None | None | I |
| I/L | 0.1454 | likely_benign | 0.1196 | benign | -0.338 | Destabilizing | None | N | 0.261 | neutral | N | 0.430977247 | None | None | I |
| I/M | 0.0989 | likely_benign | 0.086 | benign | -0.368 | Destabilizing | None | N | 0.241 | neutral | N | 0.464185744 | None | None | I |
| I/N | 0.1828 | likely_benign | 0.1223 | benign | -0.096 | Destabilizing | None | N | 0.236 | neutral | N | 0.439538016 | None | None | I |
| I/P | 0.9257 | likely_pathogenic | 0.8914 | pathogenic | -0.372 | Destabilizing | 0.085 | N | 0.542 | neutral | None | None | None | None | I |
| I/Q | 0.4656 | ambiguous | 0.3976 | ambiguous | -0.349 | Destabilizing | 0.044 | N | 0.581 | neutral | None | None | None | None | I |
| I/R | 0.3154 | likely_benign | 0.2664 | benign | 0.323 | Stabilizing | 0.044 | N | 0.543 | neutral | None | None | None | None | I |
| I/S | 0.2496 | likely_benign | 0.1868 | benign | -0.525 | Destabilizing | 0.007 | N | 0.444 | neutral | N | 0.476152177 | None | None | I |
| I/T | 0.1612 | likely_benign | 0.1172 | benign | -0.528 | Destabilizing | 0.014 | N | 0.399 | neutral | N | 0.508475239 | None | None | I |
| I/V | 0.0946 | likely_benign | 0.0812 | benign | -0.372 | Destabilizing | None | N | 0.127 | neutral | N | 0.419989463 | None | None | I |
| I/W | 0.5337 | ambiguous | 0.5266 | ambiguous | -0.644 | Destabilizing | 0.245 | N | 0.518 | neutral | None | None | None | None | I |
| I/Y | 0.2084 | likely_benign | 0.2033 | benign | -0.385 | Destabilizing | None | N | 0.152 | 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.