Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32285 | 97078;97079;97080 | chr2:178543120;178543119;178543118 | chr2:179407847;179407846;179407845 |
| N2AB | 30644 | 92155;92156;92157 | chr2:178543120;178543119;178543118 | chr2:179407847;179407846;179407845 |
| N2A | 29717 | 89374;89375;89376 | chr2:178543120;178543119;178543118 | chr2:179407847;179407846;179407845 |
| N2B | 23220 | 69883;69884;69885 | chr2:178543120;178543119;178543118 | chr2:179407847;179407846;179407845 |
| Novex-1 | 23345 | 70258;70259;70260 | chr2:178543120;178543119;178543118 | chr2:179407847;179407846;179407845 |
| Novex-2 | 23412 | 70459;70460;70461 | chr2:178543120;178543119;178543118 | chr2:179407847;179407846;179407845 |
| 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 | rs878898914  |
-1.804 | 0.002 | N | 0.243 | 0.083 | None | gnomAD-2.1.1 | 3.22E-05 | None | None | None | None | I | None | 1.15902E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/A | rs878898914 |
-1.804 | 0.002 | N | 0.243 | 0.083 | None | gnomAD-3.1.2 | 1.99E-05 | None | None | None | None | I | None | 7.33E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/M | rs747046501 |
-0.946 | 0.009 | N | 0.468 | 0.066 | 0.18274738541 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.11284E-04 | None | 3.28E-05 | None | 0 | 8.89E-06 | 0 |
| V/M | rs747046501 |
-0.946 | 0.009 | N | 0.468 | 0.066 | 0.18274738541 | gnomAD-3.1.2 | 6.6E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.08594E-04 | 0 |
| V/M | rs747046501 |
-0.946 | 0.009 | N | 0.468 | 0.066 | 0.18274738541 | gnomAD-4.0.0 | 5.14767E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 7.28757E-05 | None | 0 | 0 | 0 | 1.34246E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.173 | likely_benign | 0.1584 | benign | -1.442 | Destabilizing | 0.002 | N | 0.243 | neutral | N | 0.448597429 | None | None | I |
| V/C | 0.6323 | likely_pathogenic | 0.6205 | pathogenic | -1.073 | Destabilizing | 0.935 | D | 0.572 | neutral | None | None | None | None | I |
| V/D | 0.3263 | likely_benign | 0.3124 | benign | -1.387 | Destabilizing | 0.38 | N | 0.665 | neutral | None | None | None | None | I |
| V/E | 0.2808 | likely_benign | 0.2499 | benign | -1.44 | Destabilizing | 0.117 | N | 0.66 | neutral | N | 0.490558695 | None | None | I |
| V/F | 0.1274 | likely_benign | 0.1214 | benign | -1.329 | Destabilizing | 0.38 | N | 0.599 | neutral | None | None | None | None | I |
| V/G | 0.2134 | likely_benign | 0.2093 | benign | -1.689 | Destabilizing | 0.117 | N | 0.618 | neutral | N | 0.466009506 | None | None | I |
| V/H | 0.5575 | ambiguous | 0.5442 | ambiguous | -1.083 | Destabilizing | 0.935 | D | 0.653 | neutral | None | None | None | None | I |
| V/I | 0.0681 | likely_benign | 0.0652 | benign | -0.883 | Destabilizing | 0.081 | N | 0.494 | neutral | None | None | None | None | I |
| V/K | 0.4277 | ambiguous | 0.4152 | ambiguous | -1.067 | Destabilizing | 0.149 | N | 0.658 | neutral | None | None | None | None | I |
| V/L | 0.1446 | likely_benign | 0.1403 | benign | -0.883 | Destabilizing | 0.009 | N | 0.518 | neutral | N | 0.468913986 | None | None | I |
| V/M | 0.1261 | likely_benign | 0.1166 | benign | -0.667 | Destabilizing | 0.009 | N | 0.468 | neutral | N | 0.498852891 | None | None | I |
| V/N | 0.2383 | likely_benign | 0.2304 | benign | -0.847 | Destabilizing | 0.38 | N | 0.665 | neutral | None | None | None | None | I |
| V/P | 0.4175 | ambiguous | 0.458 | ambiguous | -1.036 | Destabilizing | 0.555 | D | 0.661 | neutral | None | None | None | None | I |
| V/Q | 0.335 | likely_benign | 0.3351 | benign | -1.145 | Destabilizing | 0.38 | N | 0.665 | neutral | None | None | None | None | I |
| V/R | 0.3705 | ambiguous | 0.3837 | ambiguous | -0.441 | Destabilizing | 0.38 | N | 0.667 | neutral | None | None | None | None | I |
| V/S | 0.188 | likely_benign | 0.1828 | benign | -1.328 | Destabilizing | 0.007 | N | 0.484 | neutral | None | None | None | None | I |
| V/T | 0.1778 | likely_benign | 0.1635 | benign | -1.283 | Destabilizing | 0.002 | N | 0.291 | neutral | None | None | None | None | I |
| V/W | 0.6801 | likely_pathogenic | 0.6808 | pathogenic | -1.391 | Destabilizing | 0.935 | D | 0.698 | prob.neutral | None | None | None | None | I |
| V/Y | 0.4107 | ambiguous | 0.4162 | ambiguous | -1.122 | Destabilizing | 0.555 | D | 0.585 | 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.