Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2772 | 8539;8540;8541 | chr2:178770478;178770477;178770476 | chr2:179635205;179635204;179635203 |
| N2AB | 2772 | 8539;8540;8541 | chr2:178770478;178770477;178770476 | chr2:179635205;179635204;179635203 |
| N2A | 2772 | 8539;8540;8541 | chr2:178770478;178770477;178770476 | chr2:179635205;179635204;179635203 |
| N2B | 2726 | 8401;8402;8403 | chr2:178770478;178770477;178770476 | chr2:179635205;179635204;179635203 |
| Novex-1 | 2726 | 8401;8402;8403 | chr2:178770478;178770477;178770476 | chr2:179635205;179635204;179635203 |
| Novex-2 | 2726 | 8401;8402;8403 | chr2:178770478;178770477;178770476 | chr2:179635205;179635204;179635203 |
| Novex-3 | 2772 | 8539;8540;8541 | chr2:178770478;178770477;178770476 | chr2:179635205;179635204;179635203 |
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/M | rs143035953  |
-0.118 | 0.013 | D | 0.138 | 0.14 | None | gnomAD-2.1.1 | 4.25047E-04 | None | None | None | None | I | None | 4.165E-03 | 8.47E-05 | None | 0 | 3.01356E-04 | None | 1.30659E-04 | None | 0 | 1.55E-05 | 1.38581E-04 |
| V/M | rs143035953 |
-0.118 | 0.013 | D | 0.138 | 0.14 | None | gnomAD-3.1.2 | 1.03833E-03 | None | None | None | None | I | None | 3.54713E-03 | 3.27182E-04 | 0 | 0 | 5.77367E-04 | None | 0 | 0 | 1.47E-05 | 2.07125E-04 | 4.79386E-04 |
| V/M | rs143035953 |
-0.118 | 0.013 | D | 0.138 | 0.14 | None | 1000 genomes | 9.98403E-04 | None | None | None | None | I | None | 3E-03 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| V/M | rs143035953 |
-0.118 | 0.013 | D | 0.138 | 0.14 | None | gnomAD-4.0.0 | 2.46573E-04 | None | None | None | None | I | None | 4.10426E-03 | 1.4995E-04 | None | 0 | 5.34926E-04 | None | 0 | 0 | 2.54238E-05 | 1.42729E-04 | 2.23993E-04 |
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 | 0.0718 | likely_benign | 0.0765 | benign | -0.34 | Destabilizing | None | N | 0.079 | neutral | N | 0.428511383 | None | None | I |
| V/C | 0.5613 | ambiguous | 0.5755 | pathogenic | -0.736 | Destabilizing | 0.356 | N | 0.201 | neutral | None | None | None | None | I |
| V/D | 0.1668 | likely_benign | 0.1625 | benign | -0.285 | Destabilizing | 0.072 | N | 0.296 | neutral | None | None | None | None | I |
| V/E | 0.1529 | likely_benign | 0.1453 | benign | -0.406 | Destabilizing | 0.012 | N | 0.221 | neutral | N | 0.412240776 | None | None | I |
| V/F | 0.1272 | likely_benign | 0.1454 | benign | -0.691 | Destabilizing | 0.214 | N | 0.303 | neutral | None | None | None | None | I |
| V/G | 0.0997 | likely_benign | 0.1076 | benign | -0.415 | Destabilizing | None | N | 0.147 | neutral | N | 0.482997109 | None | None | I |
| V/H | 0.3269 | likely_benign | 0.3255 | benign | 0.01 | Stabilizing | 0.356 | N | 0.254 | neutral | None | None | None | None | I |
| V/I | 0.0729 | likely_benign | 0.0789 | benign | -0.294 | Destabilizing | 0.016 | N | 0.211 | neutral | None | None | None | None | I |
| V/K | 0.2032 | likely_benign | 0.1821 | benign | -0.347 | Destabilizing | 0.016 | N | 0.197 | neutral | None | None | None | None | I |
| V/L | 0.1157 | likely_benign | 0.1311 | benign | -0.294 | Destabilizing | 0.005 | N | 0.195 | neutral | D | 0.524661539 | None | None | I |
| V/M | 0.0886 | likely_benign | 0.1019 | benign | -0.457 | Destabilizing | 0.013 | N | 0.138 | neutral | D | 0.541746056 | None | None | I |
| V/N | 0.1142 | likely_benign | 0.1214 | benign | -0.147 | Destabilizing | 0.072 | N | 0.329 | neutral | None | None | None | None | I |
| V/P | 0.2519 | likely_benign | 0.2378 | benign | -0.279 | Destabilizing | 0.072 | N | 0.304 | neutral | None | None | None | None | I |
| V/Q | 0.185 | likely_benign | 0.1765 | benign | -0.373 | Destabilizing | 0.001 | N | 0.118 | neutral | None | None | None | None | I |
| V/R | 0.2009 | likely_benign | 0.1757 | benign | 0.137 | Stabilizing | 0.072 | N | 0.325 | neutral | None | None | None | None | I |
| V/S | 0.0849 | likely_benign | 0.0886 | benign | -0.472 | Destabilizing | 0.016 | N | 0.223 | neutral | None | None | None | None | I |
| V/T | 0.0794 | likely_benign | 0.0839 | benign | -0.497 | Destabilizing | None | N | 0.084 | neutral | None | None | None | None | I |
| V/W | 0.6157 | likely_pathogenic | 0.6343 | pathogenic | -0.748 | Destabilizing | 0.864 | D | 0.247 | neutral | None | None | None | None | I |
| V/Y | 0.3786 | ambiguous | 0.414 | ambiguous | -0.464 | Destabilizing | 0.356 | N | 0.283 | 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.