Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22861 | 68806;68807;68808 | chr2:178577845;178577844;178577843 | chr2:179442572;179442571;179442570 |
| N2AB | 21220 | 63883;63884;63885 | chr2:178577845;178577844;178577843 | chr2:179442572;179442571;179442570 |
| N2A | 20293 | 61102;61103;61104 | chr2:178577845;178577844;178577843 | chr2:179442572;179442571;179442570 |
| N2B | 13796 | 41611;41612;41613 | chr2:178577845;178577844;178577843 | chr2:179442572;179442571;179442570 |
| Novex-1 | 13921 | 41986;41987;41988 | chr2:178577845;178577844;178577843 | chr2:179442572;179442571;179442570 |
| Novex-2 | 13988 | 42187;42188;42189 | chr2:178577845;178577844;178577843 | chr2:179442572;179442571;179442570 |
| 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/L | rs1575838768  |
None | 0.005 | N | 0.395 | 0.027 | 0.361360026772 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/L | rs1575838768 |
None | 0.005 | N | 0.395 | 0.027 | 0.361360026772 | gnomAD-4.0.0 | 6.57393E-06 | None | None | None | None | N | None | 2.41243E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | None | None | 0.062 | N | 0.431 | 0.209 | 0.469660041277 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 6.33473E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.2999 | likely_benign | 0.2735 | benign | -1.917 | Destabilizing | 0.035 | N | 0.411 | neutral | None | None | None | None | N |
| I/C | 0.567 | likely_pathogenic | 0.536 | ambiguous | -0.958 | Destabilizing | 0.824 | D | 0.527 | neutral | None | None | None | None | N |
| I/D | 0.7213 | likely_pathogenic | 0.6922 | pathogenic | -1.706 | Destabilizing | 0.555 | D | 0.615 | neutral | None | None | None | None | N |
| I/E | 0.4598 | ambiguous | 0.4705 | ambiguous | -1.608 | Destabilizing | 0.555 | D | 0.615 | neutral | None | None | None | None | N |
| I/F | 0.1709 | likely_benign | 0.1552 | benign | -1.153 | Destabilizing | 0.317 | N | 0.44 | neutral | N | 0.47328523 | None | None | N |
| I/G | 0.5916 | likely_pathogenic | 0.5451 | ambiguous | -2.336 | Highly Destabilizing | 0.555 | D | 0.604 | neutral | None | None | None | None | N |
| I/H | 0.3905 | ambiguous | 0.3661 | ambiguous | -1.65 | Destabilizing | 0.935 | D | 0.637 | neutral | None | None | None | None | N |
| I/K | 0.2516 | likely_benign | 0.2362 | benign | -1.342 | Destabilizing | 0.555 | D | 0.604 | neutral | None | None | None | None | N |
| I/L | 0.0967 | likely_benign | 0.0891 | benign | -0.781 | Destabilizing | 0.005 | N | 0.395 | neutral | N | 0.453563319 | None | None | N |
| I/M | 0.0816 | likely_benign | 0.0817 | benign | -0.539 | Destabilizing | 0.002 | N | 0.21 | neutral | N | 0.413852924 | None | None | N |
| I/N | 0.259 | likely_benign | 0.2527 | benign | -1.306 | Destabilizing | 0.741 | D | 0.619 | neutral | N | 0.444250402 | None | None | N |
| I/P | 0.9613 | likely_pathogenic | 0.9411 | pathogenic | -1.133 | Destabilizing | 0.791 | D | 0.613 | neutral | None | None | None | None | N |
| I/Q | 0.2522 | likely_benign | 0.2671 | benign | -1.369 | Destabilizing | 0.555 | D | 0.617 | neutral | None | None | None | None | N |
| I/R | 0.2014 | likely_benign | 0.1885 | benign | -0.851 | Destabilizing | 0.555 | D | 0.614 | neutral | None | None | None | None | N |
| I/S | 0.2181 | likely_benign | 0.2099 | benign | -1.941 | Destabilizing | 0.117 | N | 0.515 | neutral | N | 0.336135928 | None | None | N |
| I/T | 0.1793 | likely_benign | 0.1548 | benign | -1.726 | Destabilizing | 0.062 | N | 0.431 | neutral | N | 0.362498597 | None | None | N |
| I/V | 0.0816 | likely_benign | 0.0726 | benign | -1.133 | Destabilizing | None | N | 0.171 | neutral | N | 0.381260503 | None | None | N |
| I/W | 0.7916 | likely_pathogenic | 0.7584 | pathogenic | -1.412 | Destabilizing | 0.935 | D | 0.669 | neutral | None | None | None | None | N |
| I/Y | 0.4533 | ambiguous | 0.4486 | ambiguous | -1.135 | Destabilizing | 0.555 | D | 0.519 | 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.