Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26047 | 78364;78365;78366 | chr2:178567993;178567992;178567991 | chr2:179432720;179432719;179432718 |
| N2AB | 24406 | 73441;73442;73443 | chr2:178567993;178567992;178567991 | chr2:179432720;179432719;179432718 |
| N2A | 23479 | 70660;70661;70662 | chr2:178567993;178567992;178567991 | chr2:179432720;179432719;179432718 |
| N2B | 16982 | 51169;51170;51171 | chr2:178567993;178567992;178567991 | chr2:179432720;179432719;179432718 |
| Novex-1 | 17107 | 51544;51545;51546 | chr2:178567993;178567992;178567991 | chr2:179432720;179432719;179432718 |
| Novex-2 | 17174 | 51745;51746;51747 | chr2:178567993;178567992;178567991 | chr2:179432720;179432719;179432718 |
| 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/H | rs1315662301  |
None | 0.942 | D | 0.652 | 0.279 | 0.285698343383 | gnomAD-4.0.0 | 6.84331E-07 | None | None | None | None | I | None | 0 | 2.23704E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs1315662301 |
-0.191 | 0.942 | N | 0.545 | 0.256 | 0.233785782151 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| D/N | rs1315662301 |
-0.191 | 0.942 | N | 0.545 | 0.256 | 0.233785782151 | gnomAD-4.0.0 | 2.73732E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 4.63811E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1966 | likely_benign | 0.2175 | benign | -0.174 | Destabilizing | 0.822 | D | 0.529 | neutral | N | 0.508648597 | None | None | I |
| D/C | 0.6199 | likely_pathogenic | 0.6377 | pathogenic | -0.285 | Destabilizing | 0.998 | D | 0.652 | neutral | None | None | None | None | I |
| D/E | 0.1456 | likely_benign | 0.1512 | benign | -0.482 | Destabilizing | 0.014 | N | 0.239 | neutral | N | 0.446445345 | None | None | I |
| D/F | 0.7122 | likely_pathogenic | 0.7434 | pathogenic | 0.369 | Stabilizing | 0.915 | D | 0.683 | prob.neutral | None | None | None | None | I |
| D/G | 0.1391 | likely_benign | 0.1464 | benign | -0.476 | Destabilizing | 0.822 | D | 0.587 | neutral | N | 0.507379161 | None | None | I |
| D/H | 0.335 | likely_benign | 0.3489 | ambiguous | 0.567 | Stabilizing | 0.942 | D | 0.652 | neutral | D | 0.523810051 | None | None | I |
| D/I | 0.5805 | likely_pathogenic | 0.6242 | pathogenic | 0.607 | Stabilizing | 0.956 | D | 0.677 | prob.neutral | None | None | None | None | I |
| D/K | 0.4304 | ambiguous | 0.4603 | ambiguous | None | Stabilizing | 0.915 | D | 0.588 | neutral | None | None | None | None | I |
| D/L | 0.5326 | ambiguous | 0.5722 | pathogenic | 0.607 | Stabilizing | 0.915 | D | 0.671 | neutral | None | None | None | None | I |
| D/M | 0.6797 | likely_pathogenic | 0.7096 | pathogenic | 0.575 | Stabilizing | 0.998 | D | 0.645 | neutral | None | None | None | None | I |
| D/N | 0.1008 | likely_benign | 0.1044 | benign | -0.562 | Destabilizing | 0.942 | D | 0.545 | neutral | N | 0.508859241 | None | None | I |
| D/P | 0.927 | likely_pathogenic | 0.9384 | pathogenic | 0.371 | Stabilizing | 0.978 | D | 0.665 | neutral | None | None | None | None | I |
| D/Q | 0.3359 | likely_benign | 0.3555 | ambiguous | -0.427 | Destabilizing | 0.915 | D | 0.604 | neutral | None | None | None | None | I |
| D/R | 0.4893 | ambiguous | 0.521 | ambiguous | 0.395 | Stabilizing | 0.956 | D | 0.657 | neutral | None | None | None | None | I |
| D/S | 0.1153 | likely_benign | 0.1234 | benign | -0.73 | Destabilizing | 0.86 | D | 0.531 | neutral | None | None | None | None | I |
| D/T | 0.2314 | likely_benign | 0.2523 | benign | -0.47 | Destabilizing | 0.956 | D | 0.615 | neutral | None | None | None | None | I |
| D/V | 0.3755 | ambiguous | 0.4092 | ambiguous | 0.371 | Stabilizing | 0.942 | D | 0.673 | neutral | N | 0.514017131 | None | None | I |
| D/W | 0.9486 | likely_pathogenic | 0.9555 | pathogenic | 0.566 | Stabilizing | 0.994 | D | 0.661 | neutral | None | None | None | None | I |
| D/Y | 0.3744 | ambiguous | 0.3968 | ambiguous | 0.634 | Stabilizing | 0.032 | N | 0.407 | neutral | N | 0.489295229 | 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.