Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 8538 | 25837;25838;25839 | chr2:178717122;178717121;178717120 | chr2:179581849;179581848;179581847 |
| N2AB | 8221 | 24886;24887;24888 | chr2:178717122;178717121;178717120 | chr2:179581849;179581848;179581847 |
| N2A | 7294 | 22105;22106;22107 | chr2:178717122;178717121;178717120 | chr2:179581849;179581848;179581847 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | None | None | None | N | 0.159 | 0.267 | 0.263140351381 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| S/F | rs375170912  |
-0.841 | 0.991 | D | 0.571 | 0.4 | None | gnomAD-2.1.1 | 2.15E-05 | None | None | None | None | I | None | 2.48077E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/F | rs375170912 |
-0.841 | 0.991 | D | 0.571 | 0.4 | None | gnomAD-3.1.2 | 7.23E-05 | None | None | None | None | I | None | 2.6529E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/F | rs375170912 |
-0.841 | 0.991 | D | 0.571 | 0.4 | None | gnomAD-4.0.0 | 9.29889E-06 | None | None | None | None | I | None | 2.00288E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0892 | likely_benign | 0.0889 | benign | -0.729 | Destabilizing | None | N | 0.159 | neutral | N | 0.502368687 | None | None | I |
| S/C | 0.1774 | likely_benign | 0.1933 | benign | -0.33 | Destabilizing | 0.997 | D | 0.532 | neutral | D | 0.54973292 | None | None | I |
| S/D | 0.6332 | likely_pathogenic | 0.6371 | pathogenic | 0.057 | Stabilizing | 0.852 | D | 0.414 | neutral | None | None | None | None | I |
| S/E | 0.6455 | likely_pathogenic | 0.6471 | pathogenic | 0.053 | Stabilizing | 0.624 | D | 0.477 | neutral | None | None | None | None | I |
| S/F | 0.1426 | likely_benign | 0.1597 | benign | -0.882 | Destabilizing | 0.991 | D | 0.571 | neutral | D | 0.534830413 | None | None | I |
| S/G | 0.1705 | likely_benign | 0.1686 | benign | -0.977 | Destabilizing | 0.687 | D | 0.477 | neutral | None | None | None | None | I |
| S/H | 0.3592 | ambiguous | 0.3775 | ambiguous | -1.352 | Destabilizing | 0.993 | D | 0.539 | neutral | None | None | None | None | I |
| S/I | 0.1636 | likely_benign | 0.1719 | benign | -0.175 | Destabilizing | 0.987 | D | 0.572 | neutral | None | None | None | None | I |
| S/K | 0.7373 | likely_pathogenic | 0.7463 | pathogenic | -0.627 | Destabilizing | 0.223 | N | 0.209 | neutral | None | None | None | None | I |
| S/L | 0.1163 | likely_benign | 0.1215 | benign | -0.175 | Destabilizing | 0.955 | D | 0.508 | neutral | None | None | None | None | I |
| S/M | 0.2022 | likely_benign | 0.2061 | benign | 0.022 | Stabilizing | 0.998 | D | 0.537 | neutral | None | None | None | None | I |
| S/N | 0.207 | likely_benign | 0.2107 | benign | -0.495 | Destabilizing | 0.577 | D | 0.427 | neutral | None | None | None | None | I |
| S/P | 0.9271 | likely_pathogenic | 0.9351 | pathogenic | -0.326 | Destabilizing | 0.969 | D | 0.549 | neutral | D | 0.549225941 | None | None | I |
| S/Q | 0.5295 | ambiguous | 0.5417 | ambiguous | -0.597 | Destabilizing | 0.455 | N | 0.315 | neutral | None | None | None | None | I |
| S/R | 0.606 | likely_pathogenic | 0.6135 | pathogenic | -0.528 | Destabilizing | 0.915 | D | 0.459 | neutral | None | None | None | None | I |
| S/T | 0.084 | likely_benign | 0.0842 | benign | -0.542 | Destabilizing | 0.337 | N | 0.444 | neutral | N | 0.495826521 | None | None | I |
| S/V | 0.1707 | likely_benign | 0.1775 | benign | -0.326 | Destabilizing | 0.801 | D | 0.501 | neutral | None | None | None | None | I |
| S/W | 0.3726 | ambiguous | 0.4115 | ambiguous | -0.875 | Destabilizing | 0.999 | D | 0.621 | neutral | None | None | None | None | I |
| S/Y | 0.1731 | likely_benign | 0.1917 | benign | -0.62 | Destabilizing | 0.997 | D | 0.572 | neutral | N | 0.510143822 | 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.