Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27246 | 81961;81962;81963 | chr2:178564396;178564395;178564394 | chr2:179429123;179429122;179429121 |
| N2AB | 25605 | 77038;77039;77040 | chr2:178564396;178564395;178564394 | chr2:179429123;179429122;179429121 |
| N2A | 24678 | 74257;74258;74259 | chr2:178564396;178564395;178564394 | chr2:179429123;179429122;179429121 |
| N2B | 18181 | 54766;54767;54768 | chr2:178564396;178564395;178564394 | chr2:179429123;179429122;179429121 |
| Novex-1 | 18306 | 55141;55142;55143 | chr2:178564396;178564395;178564394 | chr2:179429123;179429122;179429121 |
| Novex-2 | 18373 | 55342;55343;55344 | chr2:178564396;178564395;178564394 | chr2:179429123;179429122;179429121 |
| 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 | rs367603381  |
-2.785 | 0.983 | N | 0.737 | 0.343 | None | gnomAD-2.1.1 | 3.22E-05 | None | None | None | None | N | None | 1.24069E-04 | 8.51E-05 | None | 0 | 0 | None | 0 | None | 0 | 1.57E-05 | 1.40964E-04 |
| I/T | rs367603381 |
-2.785 | 0.983 | N | 0.737 | 0.343 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 2.41E-05 | 1.31096E-04 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| I/T | rs367603381 |
-2.785 | 0.983 | N | 0.737 | 0.343 | None | gnomAD-4.0.0 | 2.04534E-05 | None | None | None | None | N | None | 6.67521E-05 | 1.1678E-04 | None | 0 | 2.23434E-05 | None | 1.56328E-05 | 0 | 1.52577E-05 | 0 | 1.60143E-05 |
| I/V | None | None | 0.598 | N | 0.492 | 0.116 | 0.451692371253 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.5642 | likely_pathogenic | 0.4971 | ambiguous | -2.792 | Highly Destabilizing | 0.916 | D | 0.7 | prob.neutral | None | None | None | None | N |
| I/C | 0.7983 | likely_pathogenic | 0.786 | pathogenic | -2.101 | Highly Destabilizing | 0.999 | D | 0.751 | deleterious | None | None | None | None | N |
| I/D | 0.9846 | likely_pathogenic | 0.9776 | pathogenic | -3.313 | Highly Destabilizing | 0.996 | D | 0.847 | deleterious | None | None | None | None | N |
| I/E | 0.9298 | likely_pathogenic | 0.9102 | pathogenic | -3.109 | Highly Destabilizing | 0.996 | D | 0.836 | deleterious | None | None | None | None | N |
| I/F | 0.1855 | likely_benign | 0.1616 | benign | -1.632 | Destabilizing | 0.025 | N | 0.544 | neutral | N | 0.456566338 | None | None | N |
| I/G | 0.9317 | likely_pathogenic | 0.9058 | pathogenic | -3.284 | Highly Destabilizing | 0.987 | D | 0.815 | deleterious | None | None | None | None | N |
| I/H | 0.7943 | likely_pathogenic | 0.7456 | pathogenic | -2.675 | Highly Destabilizing | 0.999 | D | 0.821 | deleterious | None | None | None | None | N |
| I/K | 0.6657 | likely_pathogenic | 0.6015 | pathogenic | -2.135 | Highly Destabilizing | 0.987 | D | 0.845 | deleterious | None | None | None | None | N |
| I/L | 0.1633 | likely_benign | 0.1512 | benign | -1.36 | Destabilizing | 0.426 | N | 0.497 | neutral | N | 0.494391221 | None | None | N |
| I/M | 0.1272 | likely_benign | 0.1165 | benign | -1.42 | Destabilizing | 0.983 | D | 0.752 | deleterious | N | 0.473192437 | None | None | N |
| I/N | 0.8092 | likely_pathogenic | 0.75 | pathogenic | -2.458 | Highly Destabilizing | 0.994 | D | 0.865 | deleterious | N | 0.497524436 | None | None | N |
| I/P | 0.9938 | likely_pathogenic | 0.9914 | pathogenic | -1.821 | Destabilizing | 0.996 | D | 0.861 | deleterious | None | None | None | None | N |
| I/Q | 0.7708 | likely_pathogenic | 0.7256 | pathogenic | -2.357 | Highly Destabilizing | 0.999 | D | 0.845 | deleterious | None | None | None | None | N |
| I/R | 0.5275 | ambiguous | 0.4505 | ambiguous | -1.767 | Destabilizing | 0.996 | D | 0.863 | deleterious | None | None | None | None | N |
| I/S | 0.5934 | likely_pathogenic | 0.5271 | ambiguous | -3.072 | Highly Destabilizing | 0.983 | D | 0.749 | deleterious | N | 0.495911373 | None | None | N |
| I/T | 0.2228 | likely_benign | 0.1846 | benign | -2.744 | Highly Destabilizing | 0.983 | D | 0.737 | prob.delet. | N | 0.477170897 | None | None | N |
| I/V | 0.1145 | likely_benign | 0.1082 | benign | -1.821 | Destabilizing | 0.598 | D | 0.492 | neutral | N | 0.495660657 | None | None | N |
| I/W | 0.8093 | likely_pathogenic | 0.7735 | pathogenic | -2.025 | Highly Destabilizing | 0.999 | D | 0.814 | deleterious | None | None | None | None | N |
| I/Y | 0.6536 | likely_pathogenic | 0.6273 | pathogenic | -1.815 | Destabilizing | 0.95 | D | 0.741 | deleterious | 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.