Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2542 | 7849;7850;7851 | chr2:178773340;178773339;178773338 | chr2:179638067;179638066;179638065 |
| N2AB | 2542 | 7849;7850;7851 | chr2:178773340;178773339;178773338 | chr2:179638067;179638066;179638065 |
| N2A | 2542 | 7849;7850;7851 | chr2:178773340;178773339;178773338 | chr2:179638067;179638066;179638065 |
| N2B | 2496 | 7711;7712;7713 | chr2:178773340;178773339;178773338 | chr2:179638067;179638066;179638065 |
| Novex-1 | 2496 | 7711;7712;7713 | chr2:178773340;178773339;178773338 | chr2:179638067;179638066;179638065 |
| Novex-2 | 2496 | 7711;7712;7713 | chr2:178773340;178773339;178773338 | chr2:179638067;179638066;179638065 |
| Novex-3 | 2542 | 7849;7850;7851 | chr2:178773340;178773339;178773338 | chr2:179638067;179638066;179638065 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/I | rs762722498  |
-0.36 | None | N | 0.101 | 0.098 | 0.385906861911 | gnomAD-2.1.1 | 4E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| L/I | rs762722498 |
-0.36 | None | N | 0.101 | 0.098 | 0.385906861911 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07383E-04 | 0 |
| L/I | rs762722498 |
-0.36 | None | N | 0.101 | 0.098 | 0.385906861911 | gnomAD-4.0.0 | 1.85896E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 3.29402E-05 | 0 |
| L/P | None | None | 0.106 | N | 0.5 | 0.381 | 0.655220577254 | gnomAD-4.0.0 | 1.59082E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85669E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.1107 | likely_benign | 0.1185 | benign | -1.408 | Destabilizing | 0.007 | N | 0.241 | neutral | None | None | None | None | N |
| L/C | 0.273 | likely_benign | 0.2857 | benign | -1.033 | Destabilizing | 0.001 | N | 0.231 | neutral | None | None | None | None | N |
| L/D | 0.3905 | ambiguous | 0.3935 | ambiguous | -0.479 | Destabilizing | 0.072 | N | 0.457 | neutral | None | None | None | None | N |
| L/E | 0.1737 | likely_benign | 0.1621 | benign | -0.467 | Destabilizing | 0.016 | N | 0.395 | neutral | None | None | None | None | N |
| L/F | 0.1088 | likely_benign | 0.1126 | benign | -0.906 | Destabilizing | 0.171 | N | 0.342 | neutral | N | 0.502784988 | None | None | N |
| L/G | 0.3596 | ambiguous | 0.3778 | ambiguous | -1.729 | Destabilizing | 0.016 | N | 0.385 | neutral | None | None | None | None | N |
| L/H | 0.133 | likely_benign | 0.1352 | benign | -0.861 | Destabilizing | 0.295 | N | 0.415 | neutral | N | 0.518458649 | None | None | N |
| L/I | 0.0531 | likely_benign | 0.0543 | benign | -0.607 | Destabilizing | None | N | 0.101 | neutral | N | 0.406554672 | None | None | N |
| L/K | 0.1221 | likely_benign | 0.1175 | benign | -0.895 | Destabilizing | None | N | 0.195 | neutral | None | None | None | None | N |
| L/M | 0.0655 | likely_benign | 0.0703 | benign | -0.627 | Destabilizing | 0.214 | N | 0.333 | neutral | None | None | None | None | N |
| L/N | 0.1659 | likely_benign | 0.168 | benign | -0.721 | Destabilizing | 0.038 | N | 0.456 | neutral | None | None | None | None | N |
| L/P | 0.8479 | likely_pathogenic | 0.8198 | pathogenic | -0.842 | Destabilizing | 0.106 | N | 0.5 | neutral | N | 0.518458649 | None | None | N |
| L/Q | 0.0882 | likely_benign | 0.0866 | benign | -0.833 | Destabilizing | 0.072 | N | 0.475 | neutral | None | None | None | None | N |
| L/R | 0.117 | likely_benign | 0.12 | benign | -0.388 | Destabilizing | None | N | 0.215 | neutral | N | 0.452456634 | None | None | N |
| L/S | 0.1181 | likely_benign | 0.1192 | benign | -1.393 | Destabilizing | 0.001 | N | 0.281 | neutral | None | None | None | None | N |
| L/T | 0.0745 | likely_benign | 0.0787 | benign | -1.247 | Destabilizing | None | N | 0.193 | neutral | None | None | None | None | N |
| L/V | 0.0588 | likely_benign | 0.0613 | benign | -0.842 | Destabilizing | 0.002 | N | 0.269 | neutral | N | 0.384123304 | None | None | N |
| L/W | 0.2401 | likely_benign | 0.2322 | benign | -0.928 | Destabilizing | 0.864 | D | 0.401 | neutral | None | None | None | None | N |
| L/Y | 0.2289 | likely_benign | 0.2308 | benign | -0.717 | Destabilizing | 0.356 | N | 0.447 | 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.