Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18800 | 56623;56624;56625 | chr2:178599395;178599394;178599393 | chr2:179464122;179464121;179464120 |
| N2AB | 17159 | 51700;51701;51702 | chr2:178599395;178599394;178599393 | chr2:179464122;179464121;179464120 |
| N2A | 16232 | 48919;48920;48921 | chr2:178599395;178599394;178599393 | chr2:179464122;179464121;179464120 |
| N2B | 9735 | 29428;29429;29430 | chr2:178599395;178599394;178599393 | chr2:179464122;179464121;179464120 |
| Novex-1 | 9860 | 29803;29804;29805 | chr2:178599395;178599394;178599393 | chr2:179464122;179464121;179464120 |
| Novex-2 | 9927 | 30004;30005;30006 | chr2:178599395;178599394;178599393 | chr2:179464122;179464121;179464120 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/Y | rs764411398  |
-0.36 | 0.99 | N | 0.611 | 0.451 | 0.586694575381 | gnomAD-2.1.1 | 1.85E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 5.06E-05 | 2.98E-05 | 0 |
| D/Y | rs764411398 |
-0.36 | 0.99 | N | 0.611 | 0.451 | 0.586694575381 | gnomAD-4.0.0 | 1.69422E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.92864E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2262 | likely_benign | 0.2523 | benign | -0.472 | Destabilizing | 0.698 | D | 0.457 | neutral | N | 0.506707157 | None | None | N |
| D/C | 0.6592 | likely_pathogenic | 0.6742 | pathogenic | 0.089 | Stabilizing | 0.998 | D | 0.655 | neutral | None | None | None | None | N |
| D/E | 0.1141 | likely_benign | 0.1156 | benign | -0.574 | Destabilizing | 0.006 | N | 0.169 | neutral | N | 0.428342374 | None | None | N |
| D/F | 0.6307 | likely_pathogenic | 0.645 | pathogenic | -0.667 | Destabilizing | 0.993 | D | 0.612 | neutral | None | None | None | None | N |
| D/G | 0.2003 | likely_benign | 0.22 | benign | -0.695 | Destabilizing | 0.822 | D | 0.498 | neutral | N | 0.509592747 | None | None | N |
| D/H | 0.3275 | likely_benign | 0.3524 | ambiguous | -0.881 | Destabilizing | 0.992 | D | 0.485 | neutral | N | 0.494855368 | None | None | N |
| D/I | 0.4592 | ambiguous | 0.4796 | ambiguous | 0.079 | Stabilizing | 0.978 | D | 0.617 | neutral | None | None | None | None | N |
| D/K | 0.4223 | ambiguous | 0.4246 | ambiguous | 0.135 | Stabilizing | 0.754 | D | 0.475 | neutral | None | None | None | None | N |
| D/L | 0.4099 | ambiguous | 0.4193 | ambiguous | 0.079 | Stabilizing | 0.956 | D | 0.611 | neutral | None | None | None | None | N |
| D/M | 0.5888 | likely_pathogenic | 0.609 | pathogenic | 0.509 | Stabilizing | 0.998 | D | 0.597 | neutral | None | None | None | None | N |
| D/N | 0.1091 | likely_benign | 0.1074 | benign | -0.105 | Destabilizing | 0.822 | D | 0.545 | neutral | N | 0.466935261 | None | None | N |
| D/P | 0.8812 | likely_pathogenic | 0.9208 | pathogenic | -0.082 | Destabilizing | 0.978 | D | 0.507 | neutral | None | None | None | None | N |
| D/Q | 0.2894 | likely_benign | 0.3018 | benign | -0.099 | Destabilizing | 0.915 | D | 0.472 | neutral | None | None | None | None | N |
| D/R | 0.4761 | ambiguous | 0.4934 | ambiguous | 0.091 | Stabilizing | 0.956 | D | 0.575 | neutral | None | None | None | None | N |
| D/S | 0.1311 | likely_benign | 0.1339 | benign | -0.257 | Destabilizing | 0.754 | D | 0.485 | neutral | None | None | None | None | N |
| D/T | 0.2154 | likely_benign | 0.224 | benign | -0.081 | Destabilizing | 0.956 | D | 0.437 | neutral | None | None | None | None | N |
| D/V | 0.2869 | likely_benign | 0.3034 | benign | -0.082 | Destabilizing | 0.942 | D | 0.595 | neutral | N | 0.480802987 | None | None | N |
| D/W | 0.8686 | likely_pathogenic | 0.8838 | pathogenic | -0.596 | Destabilizing | 0.998 | D | 0.655 | neutral | None | None | None | None | N |
| D/Y | 0.3055 | likely_benign | 0.2907 | benign | -0.439 | Destabilizing | 0.99 | D | 0.611 | neutral | N | 0.503262108 | 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.