Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1355 | 4288;4289;4290 | chr2:178779019;178779018;178779017 | chr2:179643746;179643745;179643744 |
| N2AB | 1355 | 4288;4289;4290 | chr2:178779019;178779018;178779017 | chr2:179643746;179643745;179643744 |
| N2A | 1355 | 4288;4289;4290 | chr2:178779019;178779018;178779017 | chr2:179643746;179643745;179643744 |
| N2B | 1309 | 4150;4151;4152 | chr2:178779019;178779018;178779017 | chr2:179643746;179643745;179643744 |
| Novex-1 | 1309 | 4150;4151;4152 | chr2:178779019;178779018;178779017 | chr2:179643746;179643745;179643744 |
| Novex-2 | 1309 | 4150;4151;4152 | chr2:178779019;178779018;178779017 | chr2:179643746;179643745;179643744 |
| Novex-3 | 1355 | 4288;4289;4290 | chr2:178779019;178779018;178779017 | chr2:179643746;179643745;179643744 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/I | rs1561322407  |
-0.405 | 0.811 | N | 0.447 | 0.232 | 0.498001352042 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.45E-05 | None | 0 | None | 0 | 0 | 0 |
| L/I | rs1561322407 |
-0.405 | 0.811 | N | 0.447 | 0.232 | 0.498001352042 | gnomAD-4.0.0 | 4.78882E-06 | None | None | None | None | I | None | 2.98829E-05 | 0 | None | 0 | 7.56201E-05 | None | 0 | 3.46741E-04 | 8.99332E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.4041 | ambiguous | 0.4424 | ambiguous | -1.49 | Destabilizing | 0.034 | N | 0.328 | neutral | None | None | None | None | I |
| L/C | 0.7605 | likely_pathogenic | 0.7836 | pathogenic | -0.865 | Destabilizing | 0.999 | D | 0.609 | neutral | None | None | None | None | I |
| L/D | 0.8473 | likely_pathogenic | 0.8712 | pathogenic | -0.916 | Destabilizing | 0.976 | D | 0.703 | prob.neutral | None | None | None | None | I |
| L/E | 0.4444 | ambiguous | 0.4918 | ambiguous | -0.937 | Destabilizing | 0.952 | D | 0.588 | neutral | None | None | None | None | I |
| L/F | 0.2289 | likely_benign | 0.2454 | benign | -1.053 | Destabilizing | 0.059 | N | 0.331 | neutral | N | 0.487572841 | None | None | I |
| L/G | 0.6808 | likely_pathogenic | 0.7165 | pathogenic | -1.785 | Destabilizing | 0.952 | D | 0.589 | neutral | None | None | None | None | I |
| L/H | 0.3472 | ambiguous | 0.3915 | ambiguous | -0.932 | Destabilizing | 0.996 | D | 0.706 | prob.neutral | N | 0.500227614 | None | None | I |
| L/I | 0.2219 | likely_benign | 0.2356 | benign | -0.77 | Destabilizing | 0.811 | D | 0.447 | neutral | N | 0.506299108 | None | None | I |
| L/K | 0.2713 | likely_benign | 0.3118 | benign | -1.058 | Destabilizing | 0.952 | D | 0.553 | neutral | None | None | None | None | I |
| L/M | 0.1693 | likely_benign | 0.1724 | benign | -0.555 | Destabilizing | 0.988 | D | 0.522 | neutral | None | None | None | None | I |
| L/N | 0.5253 | ambiguous | 0.5547 | ambiguous | -0.847 | Destabilizing | 0.988 | D | 0.707 | prob.neutral | None | None | None | None | I |
| L/P | 0.9571 | likely_pathogenic | 0.964 | pathogenic | -0.978 | Destabilizing | 0.984 | D | 0.705 | prob.neutral | D | 0.591573147 | None | None | I |
| L/Q | 0.1562 | likely_benign | 0.185 | benign | -1.05 | Destabilizing | 0.702 | D | 0.493 | neutral | None | None | None | None | I |
| L/R | 0.2237 | likely_benign | 0.2678 | benign | -0.401 | Destabilizing | 0.968 | D | 0.657 | neutral | N | 0.461941709 | None | None | I |
| L/S | 0.3858 | ambiguous | 0.4183 | ambiguous | -1.429 | Destabilizing | 0.851 | D | 0.529 | neutral | None | None | None | None | I |
| L/T | 0.3454 | ambiguous | 0.3732 | ambiguous | -1.338 | Destabilizing | 0.919 | D | 0.511 | neutral | None | None | None | None | I |
| L/V | 0.2038 | likely_benign | 0.225 | benign | -0.978 | Destabilizing | 0.811 | D | 0.482 | neutral | N | 0.484289497 | None | None | I |
| L/W | 0.5713 | likely_pathogenic | 0.6098 | pathogenic | -1.1 | Destabilizing | 0.999 | D | 0.731 | prob.delet. | None | None | None | None | I |
| L/Y | 0.5304 | ambiguous | 0.5591 | ambiguous | -0.896 | Destabilizing | 0.952 | D | 0.564 | neutral | 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.