Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16735 | 50428;50429;50430 | chr2:178612322;178612321;178612320 | chr2:179477049;179477048;179477047 |
| N2AB | 15094 | 45505;45506;45507 | chr2:178612322;178612321;178612320 | chr2:179477049;179477048;179477047 |
| N2A | 14167 | 42724;42725;42726 | chr2:178612322;178612321;178612320 | chr2:179477049;179477048;179477047 |
| N2B | 7670 | 23233;23234;23235 | chr2:178612322;178612321;178612320 | chr2:179477049;179477048;179477047 |
| Novex-1 | 7795 | 23608;23609;23610 | chr2:178612322;178612321;178612320 | chr2:179477049;179477048;179477047 |
| Novex-2 | 7862 | 23809;23810;23811 | chr2:178612322;178612321;178612320 | chr2:179477049;179477048;179477047 |
| 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/E | None | None | 0.248 | N | 0.168 | 0.089 | 0.137902524267 | gnomAD-4.0.0 | 6.84702E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99883E-07 | 0 | 0 |
| D/N | rs773927256  |
-0.258 | 0.996 | N | 0.652 | 0.224 | 0.223847106136 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | I | None | 0 | 2.91E-05 | None | 0 | 5.65E-05 | None | 0 | None | 0 | 0 | 0 |
| D/N | rs773927256 |
-0.258 | 0.996 | N | 0.652 | 0.224 | 0.223847106136 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07814E-04 | 0 |
| D/N | rs773927256 |
-0.258 | 0.996 | N | 0.652 | 0.224 | 0.223847106136 | gnomAD-4.0.0 | 1.41157E-05 | None | None | None | None | I | None | 0 | 3.3942E-05 | None | 0 | 0 | None | 0 | 0 | 9.58598E-06 | 5.36567E-05 | 2.85079E-05 |
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 | 0.3263 | likely_benign | 0.3117 | benign | -0.663 | Destabilizing | 0.961 | D | 0.64 | neutral | N | 0.472664348 | None | None | I |
| D/C | 0.8816 | likely_pathogenic | 0.8912 | pathogenic | -0.154 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | I |
| D/E | 0.1983 | likely_benign | 0.1987 | benign | -0.455 | Destabilizing | 0.248 | N | 0.168 | neutral | N | 0.36226299 | None | None | I |
| D/F | 0.8911 | likely_pathogenic | 0.8766 | pathogenic | -0.421 | Destabilizing | 0.999 | D | 0.705 | prob.neutral | None | None | None | None | I |
| D/G | 0.3804 | ambiguous | 0.3742 | ambiguous | -0.899 | Destabilizing | 0.98 | D | 0.633 | neutral | N | 0.474370221 | None | None | I |
| D/H | 0.7004 | likely_pathogenic | 0.7037 | pathogenic | -0.363 | Destabilizing | 1.0 | D | 0.653 | neutral | N | 0.501023017 | None | None | I |
| D/I | 0.6835 | likely_pathogenic | 0.6551 | pathogenic | -0.071 | Destabilizing | 0.999 | D | 0.699 | prob.neutral | None | None | None | None | I |
| D/K | 0.6832 | likely_pathogenic | 0.6985 | pathogenic | 0.066 | Stabilizing | 0.97 | D | 0.677 | prob.neutral | None | None | None | None | I |
| D/L | 0.6727 | likely_pathogenic | 0.6571 | pathogenic | -0.071 | Destabilizing | 0.996 | D | 0.667 | neutral | None | None | None | None | I |
| D/M | 0.8511 | likely_pathogenic | 0.8444 | pathogenic | 0.22 | Stabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | I |
| D/N | 0.1968 | likely_benign | 0.1972 | benign | -0.351 | Destabilizing | 0.996 | D | 0.652 | neutral | N | 0.480709835 | None | None | I |
| D/P | 0.6381 | likely_pathogenic | 0.6427 | pathogenic | -0.247 | Destabilizing | 0.041 | N | 0.297 | neutral | None | None | None | None | I |
| D/Q | 0.5974 | likely_pathogenic | 0.599 | pathogenic | -0.301 | Destabilizing | 0.991 | D | 0.591 | neutral | None | None | None | None | I |
| D/R | 0.7434 | likely_pathogenic | 0.7362 | pathogenic | 0.268 | Stabilizing | 0.991 | D | 0.681 | prob.neutral | None | None | None | None | I |
| D/S | 0.2344 | likely_benign | 0.2287 | benign | -0.476 | Destabilizing | 0.97 | D | 0.568 | neutral | None | None | None | None | I |
| D/T | 0.4652 | ambiguous | 0.4475 | ambiguous | -0.283 | Destabilizing | 0.985 | D | 0.683 | prob.neutral | None | None | None | None | I |
| D/V | 0.4904 | ambiguous | 0.4668 | ambiguous | -0.247 | Destabilizing | 0.994 | D | 0.657 | neutral | N | 0.480356292 | None | None | I |
| D/W | 0.9807 | likely_pathogenic | 0.9789 | pathogenic | -0.179 | Destabilizing | 1.0 | D | 0.762 | deleterious | None | None | None | None | I |
| D/Y | 0.6521 | likely_pathogenic | 0.6325 | pathogenic | -0.162 | Destabilizing | 0.999 | D | 0.705 | prob.neutral | N | 0.50290668 | 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.