Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21748 | 65467;65468;65469 | chr2:178584309;178584308;178584307 | chr2:179449036;179449035;179449034 |
| N2AB | 20107 | 60544;60545;60546 | chr2:178584309;178584308;178584307 | chr2:179449036;179449035;179449034 |
| N2A | 19180 | 57763;57764;57765 | chr2:178584309;178584308;178584307 | chr2:179449036;179449035;179449034 |
| N2B | 12683 | 38272;38273;38274 | chr2:178584309;178584308;178584307 | chr2:179449036;179449035;179449034 |
| Novex-1 | 12808 | 38647;38648;38649 | chr2:178584309;178584308;178584307 | chr2:179449036;179449035;179449034 |
| Novex-2 | 12875 | 38848;38849;38850 | chr2:178584309;178584308;178584307 | chr2:179449036;179449035;179449034 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/H | None | None | 0.998 | N | 0.737 | 0.348 | 0.435808882951 | gnomAD-4.0.0 | 1.63916E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.79987E-05 | None | 0 | 0 | 0 | 0 | 0 |
| P/L | rs1419714561  |
-0.101 | 0.986 | N | 0.719 | 0.292 | 0.46682414995 | gnomAD-2.1.1 | 4.18E-06 | None | None | None | None | I | None | 0 | 2.99E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/L | rs1419714561 |
-0.101 | 0.986 | N | 0.719 | 0.292 | 0.46682414995 | gnomAD-4.0.0 | 6.55662E-06 | None | None | None | None | I | None | 0 | 9.40867E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | rs202009606 |
-0.395 | 0.953 | N | 0.578 | 0.235 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | rs202009606 |
-0.395 | 0.953 | N | 0.578 | 0.235 | None | gnomAD-4.0.0 | 1.87987E-06 | None | None | None | None | I | None | 4.03128E-05 | 0 | None | 0 | 0 | None | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0816 | likely_benign | 0.069 | benign | -1.059 | Destabilizing | 0.953 | D | 0.508 | neutral | N | 0.444519761 | None | None | I |
| P/C | 0.6806 | likely_pathogenic | 0.5709 | pathogenic | -0.738 | Destabilizing | 1.0 | D | 0.748 | deleterious | None | None | None | None | I |
| P/D | 0.7546 | likely_pathogenic | 0.67 | pathogenic | -0.471 | Destabilizing | 0.964 | D | 0.616 | neutral | None | None | None | None | I |
| P/E | 0.437 | ambiguous | 0.3544 | ambiguous | -0.532 | Destabilizing | 0.931 | D | 0.521 | neutral | None | None | None | None | I |
| P/F | 0.8241 | likely_pathogenic | 0.7164 | pathogenic | -0.999 | Destabilizing | 1.0 | D | 0.756 | deleterious | None | None | None | None | I |
| P/G | 0.5422 | ambiguous | 0.4356 | ambiguous | -1.292 | Destabilizing | 0.982 | D | 0.649 | prob.neutral | None | None | None | None | I |
| P/H | 0.5201 | ambiguous | 0.4094 | ambiguous | -0.779 | Destabilizing | 0.998 | D | 0.737 | deleterious | N | 0.498004961 | None | None | I |
| P/I | 0.414 | ambiguous | 0.3285 | benign | -0.562 | Destabilizing | 0.998 | D | 0.798 | deleterious | None | None | None | None | I |
| P/K | 0.6359 | likely_pathogenic | 0.5307 | ambiguous | -0.737 | Destabilizing | 0.931 | D | 0.523 | neutral | None | None | None | None | I |
| P/L | 0.2575 | likely_benign | 0.1908 | benign | -0.562 | Destabilizing | 0.986 | D | 0.719 | prob.delet. | N | 0.468718531 | None | None | I |
| P/M | 0.4303 | ambiguous | 0.3452 | ambiguous | -0.449 | Destabilizing | 1.0 | D | 0.739 | deleterious | None | None | None | None | I |
| P/N | 0.59 | likely_pathogenic | 0.489 | ambiguous | -0.455 | Destabilizing | 0.995 | D | 0.761 | deleterious | None | None | None | None | I |
| P/Q | 0.2991 | likely_benign | 0.2243 | benign | -0.669 | Destabilizing | 0.512 | D | 0.379 | neutral | None | None | None | None | I |
| P/R | 0.5279 | ambiguous | 0.4227 | ambiguous | -0.216 | Destabilizing | 0.986 | D | 0.645 | neutral | N | 0.490496543 | None | None | I |
| P/S | 0.2453 | likely_benign | 0.1787 | benign | -0.957 | Destabilizing | 0.953 | D | 0.578 | neutral | N | 0.494159147 | None | None | I |
| P/T | 0.1798 | likely_benign | 0.134 | benign | -0.906 | Destabilizing | 0.976 | D | 0.619 | neutral | N | 0.507819091 | None | None | I |
| P/V | 0.2531 | likely_benign | 0.2013 | benign | -0.691 | Destabilizing | 0.995 | D | 0.649 | prob.neutral | None | None | None | None | I |
| P/W | 0.9117 | likely_pathogenic | 0.8546 | pathogenic | -1.085 | Destabilizing | 1.0 | D | 0.673 | prob.neutral | None | None | None | None | I |
| P/Y | 0.7822 | likely_pathogenic | 0.6767 | pathogenic | -0.797 | Destabilizing | 0.998 | D | 0.797 | deleterious | None | None | 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.