Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29062 | 87409;87410;87411 | chr2:178558170;178558169;178558168 | chr2:179422897;179422896;179422895 |
| N2AB | 27421 | 82486;82487;82488 | chr2:178558170;178558169;178558168 | chr2:179422897;179422896;179422895 |
| N2A | 26494 | 79705;79706;79707 | chr2:178558170;178558169;178558168 | chr2:179422897;179422896;179422895 |
| N2B | 19997 | 60214;60215;60216 | chr2:178558170;178558169;178558168 | chr2:179422897;179422896;179422895 |
| Novex-1 | 20122 | 60589;60590;60591 | chr2:178558170;178558169;178558168 | chr2:179422897;179422896;179422895 |
| Novex-2 | 20189 | 60790;60791;60792 | chr2:178558170;178558169;178558168 | chr2:179422897;179422896;179422895 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/P | rs2154156193  |
None | 1.0 | N | 0.882 | 0.692 | 0.677966677298 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| L/V | rs1293928808 |
-1.308 | 0.999 | N | 0.545 | 0.303 | 0.405560941015 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| L/V | rs1293928808 |
-1.308 | 0.999 | N | 0.545 | 0.303 | 0.405560941015 | gnomAD-4.0.0 | 1.5915E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02371E-05 |
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 | 0.7473 | likely_pathogenic | 0.733 | pathogenic | -1.834 | Destabilizing | 0.999 | D | 0.728 | prob.delet. | None | None | None | None | N |
| L/C | 0.6866 | likely_pathogenic | 0.6818 | pathogenic | -1.408 | Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | N |
| L/D | 0.9947 | likely_pathogenic | 0.9944 | pathogenic | -1.007 | Destabilizing | 1.0 | D | 0.882 | deleterious | None | None | None | None | N |
| L/E | 0.9642 | likely_pathogenic | 0.9628 | pathogenic | -0.939 | Destabilizing | 1.0 | D | 0.874 | deleterious | None | None | None | None | N |
| L/F | 0.329 | likely_benign | 0.3366 | benign | -1.122 | Destabilizing | 1.0 | D | 0.779 | deleterious | N | 0.498500601 | None | None | N |
| L/G | 0.9534 | likely_pathogenic | 0.9496 | pathogenic | -2.233 | Highly Destabilizing | 1.0 | D | 0.87 | deleterious | None | None | None | None | N |
| L/H | 0.89 | likely_pathogenic | 0.8803 | pathogenic | -1.424 | Destabilizing | 1.0 | D | 0.85 | deleterious | N | 0.478510538 | None | None | N |
| L/I | 0.1125 | likely_benign | 0.108 | benign | -0.78 | Destabilizing | 0.999 | D | 0.552 | neutral | N | 0.469561773 | None | None | N |
| L/K | 0.9295 | likely_pathogenic | 0.9262 | pathogenic | -1.288 | Destabilizing | 1.0 | D | 0.865 | deleterious | None | None | None | None | N |
| L/M | 0.1683 | likely_benign | 0.1697 | benign | -0.786 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| L/N | 0.9711 | likely_pathogenic | 0.97 | pathogenic | -1.208 | Destabilizing | 1.0 | D | 0.883 | deleterious | None | None | None | None | N |
| L/P | 0.9899 | likely_pathogenic | 0.9875 | pathogenic | -1.101 | Destabilizing | 1.0 | D | 0.882 | deleterious | N | 0.478510538 | None | None | N |
| L/Q | 0.8203 | likely_pathogenic | 0.8049 | pathogenic | -1.273 | Destabilizing | 1.0 | D | 0.882 | deleterious | None | None | None | None | N |
| L/R | 0.8722 | likely_pathogenic | 0.8605 | pathogenic | -0.822 | Destabilizing | 1.0 | D | 0.879 | deleterious | N | 0.478257048 | None | None | N |
| L/S | 0.9271 | likely_pathogenic | 0.9229 | pathogenic | -1.962 | Destabilizing | 1.0 | D | 0.865 | deleterious | None | None | None | None | N |
| L/T | 0.7497 | likely_pathogenic | 0.7283 | pathogenic | -1.756 | Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | N |
| L/V | 0.1236 | likely_benign | 0.1092 | benign | -1.101 | Destabilizing | 0.999 | D | 0.545 | neutral | N | 0.436291775 | None | None | N |
| L/W | 0.7766 | likely_pathogenic | 0.7557 | pathogenic | -1.207 | Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| L/Y | 0.8149 | likely_pathogenic | 0.8179 | pathogenic | -0.981 | Destabilizing | 1.0 | D | 0.876 | deleterious | 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.