Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21767 | 65524;65525;65526 | chr2:178583883;178583882;178583881 | chr2:179448610;179448609;179448608 |
| N2AB | 20126 | 60601;60602;60603 | chr2:178583883;178583882;178583881 | chr2:179448610;179448609;179448608 |
| N2A | 19199 | 57820;57821;57822 | chr2:178583883;178583882;178583881 | chr2:179448610;179448609;179448608 |
| N2B | 12702 | 38329;38330;38331 | chr2:178583883;178583882;178583881 | chr2:179448610;179448609;179448608 |
| Novex-1 | 12827 | 38704;38705;38706 | chr2:178583883;178583882;178583881 | chr2:179448610;179448609;179448608 |
| Novex-2 | 12894 | 38905;38906;38907 | chr2:178583883;178583882;178583881 | chr2:179448610;179448609;179448608 |
| 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 | rs762578274  |
-0.461 | None | N | 0.147 | 0.094 | 0.501940320817 | gnomAD-2.1.1 | 2.31E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 1.24626E-04 | 1.7E-05 | 1.50376E-04 |
| I/T | rs762578274 |
-0.461 | None | N | 0.147 | 0.094 | 0.501940320817 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| I/T | rs762578274 |
-0.461 | None | N | 0.147 | 0.094 | 0.501940320817 | gnomAD-4.0.0 | 3.26701E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 7.89989E-05 | 0 | 4.03085E-05 | 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 | 0.2005 | likely_benign | 0.1692 | benign | -0.769 | Destabilizing | 0.035 | N | 0.341 | neutral | None | None | None | None | N |
| I/C | 0.694 | likely_pathogenic | 0.6361 | pathogenic | -0.76 | Destabilizing | 0.824 | D | 0.344 | neutral | None | None | None | None | N |
| I/D | 0.8166 | likely_pathogenic | 0.7803 | pathogenic | -0.045 | Destabilizing | 0.38 | N | 0.37 | neutral | None | None | None | None | N |
| I/E | 0.5999 | likely_pathogenic | 0.5644 | pathogenic | -0.112 | Destabilizing | 0.38 | N | 0.383 | neutral | None | None | None | None | N |
| I/F | 0.2047 | likely_benign | 0.1812 | benign | -0.612 | Destabilizing | 0.317 | N | 0.375 | neutral | N | 0.468268139 | None | None | N |
| I/G | 0.649 | likely_pathogenic | 0.5801 | pathogenic | -0.961 | Destabilizing | 0.149 | N | 0.391 | neutral | None | None | None | None | N |
| I/H | 0.5492 | ambiguous | 0.4951 | ambiguous | -0.125 | Destabilizing | 0.935 | D | 0.334 | neutral | None | None | None | None | N |
| I/K | 0.3146 | likely_benign | 0.2855 | benign | -0.426 | Destabilizing | 0.149 | N | 0.387 | neutral | None | None | None | None | N |
| I/L | 0.0979 | likely_benign | 0.0906 | benign | -0.372 | Destabilizing | 0.012 | N | 0.163 | neutral | N | 0.419317459 | None | None | N |
| I/M | 0.0846 | likely_benign | 0.0787 | benign | -0.466 | Destabilizing | 0.005 | N | 0.095 | neutral | N | 0.479443198 | None | None | N |
| I/N | 0.4217 | ambiguous | 0.3635 | ambiguous | -0.306 | Destabilizing | 0.317 | N | 0.372 | neutral | N | 0.508725955 | None | None | N |
| I/P | 0.8662 | likely_pathogenic | 0.8406 | pathogenic | -0.471 | Destabilizing | 0.555 | D | 0.371 | neutral | None | None | None | None | N |
| I/Q | 0.4033 | ambiguous | 0.3622 | ambiguous | -0.49 | Destabilizing | 0.555 | D | 0.379 | neutral | None | None | None | None | N |
| I/R | 0.218 | likely_benign | 0.1998 | benign | 0.122 | Stabilizing | 0.38 | N | 0.385 | neutral | None | None | None | None | N |
| I/S | 0.2776 | likely_benign | 0.2421 | benign | -0.829 | Destabilizing | 0.062 | N | 0.355 | neutral | N | 0.444479688 | None | None | N |
| I/T | 0.0798 | likely_benign | 0.0739 | benign | -0.781 | Destabilizing | None | N | 0.147 | neutral | N | 0.432955973 | None | None | N |
| I/V | 0.0809 | likely_benign | 0.0748 | benign | -0.471 | Destabilizing | None | N | 0.091 | neutral | N | 0.414565 | None | None | N |
| I/W | 0.6858 | likely_pathogenic | 0.6685 | pathogenic | -0.616 | Destabilizing | 0.935 | D | 0.367 | neutral | None | None | None | None | N |
| I/Y | 0.5767 | likely_pathogenic | 0.5361 | ambiguous | -0.381 | Destabilizing | 0.555 | D | 0.369 | 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.