Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14283 | 43072;43073;43074 | chr2:178633512;178633511;178633510 | chr2:179498239;179498238;179498237 |
| N2AB | 12642 | 38149;38150;38151 | chr2:178633512;178633511;178633510 | chr2:179498239;179498238;179498237 |
| N2A | 11715 | 35368;35369;35370 | chr2:178633512;178633511;178633510 | chr2:179498239;179498238;179498237 |
| N2B | 5218 | 15877;15878;15879 | chr2:178633512;178633511;178633510 | chr2:179498239;179498238;179498237 |
| Novex-1 | 5343 | 16252;16253;16254 | chr2:178633512;178633511;178633510 | chr2:179498239;179498238;179498237 |
| Novex-2 | 5410 | 16453;16454;16455 | chr2:178633512;178633511;178633510 | chr2:179498239;179498238;179498237 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs199684560  |
-0.44 | 0.984 | N | 0.593 | 0.428 | None | gnomAD-2.1.1 | 6.79E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 1.40854E-04 | 0 |
| R/C | rs199684560 |
-0.44 | 0.984 | N | 0.593 | 0.428 | None | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 8.83E-05 | 2.07469E-04 | 0 |
| R/C | rs199684560 |
-0.44 | 0.984 | N | 0.593 | 0.428 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| R/C | rs199684560 |
-0.44 | 0.984 | N | 0.593 | 0.428 | None | gnomAD-4.0.0 | 5.20691E-05 | None | None | None | None | N | None | 1.33401E-05 | 0 | None | 0 | 0 | None | 1.56455E-05 | 0 | 6.69731E-05 | 2.19616E-05 | 1.60133E-05 |
| R/H | rs767899169 |
-1.39 | 0.005 | N | 0.251 | 0.152 | 0.211220785272 | gnomAD-2.1.1 | 3.62E-05 | None | None | None | None | N | None | 0 | 1.74075E-04 | None | 0 | 0 | None | 9.81E-05 | None | 0 | 0 | 0 |
| R/P | None | None | 0.705 | D | 0.597 | 0.499 | 0.509642975872 | gnomAD-4.0.0 | 6.84398E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99588E-07 | 0 | 0 |
| R/S | None | None | 0.251 | N | 0.551 | 0.163 | 0.366848117066 | gnomAD-4.0.0 | 6.84414E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99601E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.4429 | ambiguous | 0.4543 | ambiguous | -0.708 | Destabilizing | 0.149 | N | 0.505 | neutral | None | None | None | None | N |
| R/C | 0.1657 | likely_benign | 0.1364 | benign | -0.66 | Destabilizing | 0.984 | D | 0.593 | neutral | N | 0.50875347 | None | None | N |
| R/D | 0.6972 | likely_pathogenic | 0.7119 | pathogenic | 0.038 | Stabilizing | 0.38 | N | 0.556 | neutral | None | None | None | None | N |
| R/E | 0.3719 | ambiguous | 0.4019 | ambiguous | 0.159 | Stabilizing | 0.081 | N | 0.46 | neutral | None | None | None | None | N |
| R/F | 0.5104 | ambiguous | 0.5054 | ambiguous | -0.587 | Destabilizing | 0.235 | N | 0.601 | neutral | None | None | None | None | N |
| R/G | 0.338 | likely_benign | 0.3124 | benign | -1.011 | Destabilizing | 0.251 | N | 0.546 | neutral | D | 0.559921488 | None | None | N |
| R/H | 0.0974 | likely_benign | 0.0912 | benign | -1.326 | Destabilizing | 0.005 | N | 0.251 | neutral | N | 0.511504695 | None | None | N |
| R/I | 0.266 | likely_benign | 0.2859 | benign | 0.1 | Stabilizing | 0.555 | D | 0.601 | neutral | None | None | None | None | N |
| R/K | 0.1435 | likely_benign | 0.1191 | benign | -0.678 | Destabilizing | 0.002 | N | 0.139 | neutral | None | None | None | None | N |
| R/L | 0.2323 | likely_benign | 0.2484 | benign | 0.1 | Stabilizing | 0.251 | N | 0.573 | neutral | N | 0.511413645 | None | None | N |
| R/M | 0.3407 | ambiguous | 0.3353 | benign | -0.241 | Destabilizing | 0.935 | D | 0.536 | neutral | None | None | None | None | N |
| R/N | 0.512 | ambiguous | 0.5332 | ambiguous | -0.165 | Destabilizing | 0.081 | N | 0.477 | neutral | None | None | None | None | N |
| R/P | 0.8566 | likely_pathogenic | 0.8569 | pathogenic | -0.148 | Destabilizing | 0.705 | D | 0.597 | neutral | D | 0.674888974 | None | None | N |
| R/Q | 0.1038 | likely_benign | 0.1053 | benign | -0.331 | Destabilizing | 0.38 | N | 0.522 | neutral | None | None | None | None | N |
| R/S | 0.4687 | ambiguous | 0.4818 | ambiguous | -0.926 | Destabilizing | 0.251 | N | 0.551 | neutral | N | 0.503766431 | None | None | N |
| R/T | 0.2653 | likely_benign | 0.2872 | benign | -0.622 | Destabilizing | 0.262 | N | 0.552 | neutral | None | None | None | None | N |
| R/V | 0.347 | ambiguous | 0.3654 | ambiguous | -0.148 | Destabilizing | 0.555 | D | 0.57 | neutral | None | None | None | None | N |
| R/W | 0.1915 | likely_benign | 0.1882 | benign | -0.272 | Destabilizing | 0.001 | N | 0.414 | neutral | None | None | None | None | N |
| R/Y | 0.3231 | likely_benign | 0.3143 | benign | 0.033 | Stabilizing | 0.235 | N | 0.567 | 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.