Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32506 | 97741;97742;97743 | chr2:178541561;178541560;178541559 | chr2:179406288;179406287;179406286 |
| N2AB | 30865 | 92818;92819;92820 | chr2:178541561;178541560;178541559 | chr2:179406288;179406287;179406286 |
| N2A | 29938 | 90037;90038;90039 | chr2:178541561;178541560;178541559 | chr2:179406288;179406287;179406286 |
| N2B | 23441 | 70546;70547;70548 | chr2:178541561;178541560;178541559 | chr2:179406288;179406287;179406286 |
| Novex-1 | 23566 | 70921;70922;70923 | chr2:178541561;178541560;178541559 | chr2:179406288;179406287;179406286 |
| Novex-2 | 23633 | 71122;71123;71124 | chr2:178541561;178541560;178541559 | chr2:179406288;179406287;179406286 |
| 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/F | rs772425779  |
-1.573 | 0.427 | N | 0.68 | 0.241 | 0.484109215787 | gnomAD-2.1.1 | 8.17E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.81E-05 | 0 |
| L/F | rs772425779 |
-1.573 | 0.427 | N | 0.68 | 0.241 | 0.484109215787 | gnomAD-4.0.0 | 4.79477E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.61178E-06 | 0 | 0 |
| L/S | None | None | 0.175 | N | 0.69 | 0.348 | 0.708633667434 | gnomAD-4.0.0 | 3.19666E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.74106E-06 | 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 | 0.4229 | ambiguous | 0.3826 | ambiguous | -2.093 | Highly Destabilizing | 0.055 | N | 0.576 | neutral | None | None | None | None | N |
| L/C | 0.5689 | likely_pathogenic | 0.5451 | ambiguous | -1.704 | Destabilizing | 0.958 | D | 0.7 | prob.neutral | None | None | None | None | N |
| L/D | 0.9706 | likely_pathogenic | 0.9732 | pathogenic | -1.497 | Destabilizing | 0.22 | N | 0.744 | deleterious | None | None | None | None | N |
| L/E | 0.8761 | likely_pathogenic | 0.8733 | pathogenic | -1.381 | Destabilizing | 0.22 | N | 0.745 | deleterious | None | None | None | None | N |
| L/F | 0.4853 | ambiguous | 0.5084 | ambiguous | -1.33 | Destabilizing | 0.427 | N | 0.68 | prob.neutral | N | 0.489309953 | None | None | N |
| L/G | 0.8184 | likely_pathogenic | 0.8086 | pathogenic | -2.531 | Highly Destabilizing | 0.22 | N | 0.725 | prob.delet. | None | None | None | None | N |
| L/H | 0.7878 | likely_pathogenic | 0.8103 | pathogenic | -1.812 | Destabilizing | 0.958 | D | 0.771 | deleterious | None | None | None | None | N |
| L/I | 0.1025 | likely_benign | 0.093 | benign | -0.894 | Destabilizing | 0.001 | N | 0.273 | neutral | N | 0.50906239 | None | None | N |
| L/K | 0.8603 | likely_pathogenic | 0.873 | pathogenic | -1.315 | Destabilizing | 0.22 | N | 0.705 | prob.neutral | None | None | None | None | N |
| L/M | 0.1985 | likely_benign | 0.1764 | benign | -1.017 | Destabilizing | 0.497 | N | 0.639 | neutral | None | None | None | None | N |
| L/N | 0.8132 | likely_pathogenic | 0.8317 | pathogenic | -1.324 | Destabilizing | 0.667 | D | 0.773 | deleterious | None | None | None | None | N |
| L/P | 0.1014 | likely_benign | 0.1295 | benign | -1.267 | Destabilizing | None | N | 0.458 | neutral | None | None | None | None | N |
| L/Q | 0.6737 | likely_pathogenic | 0.6662 | pathogenic | -1.357 | Destabilizing | 0.667 | D | 0.743 | deleterious | None | None | None | None | N |
| L/R | 0.7806 | likely_pathogenic | 0.7924 | pathogenic | -0.98 | Destabilizing | 0.667 | D | 0.743 | deleterious | None | None | None | None | N |
| L/S | 0.7348 | likely_pathogenic | 0.713 | pathogenic | -2.116 | Highly Destabilizing | 0.175 | N | 0.69 | prob.neutral | N | 0.504820542 | None | None | N |
| L/T | 0.4575 | ambiguous | 0.4224 | ambiguous | -1.86 | Destabilizing | 0.22 | N | 0.657 | neutral | None | None | None | None | N |
| L/V | 0.0914 | likely_benign | 0.0791 | benign | -1.267 | Destabilizing | 0.015 | N | 0.472 | neutral | N | 0.428923951 | None | None | N |
| L/W | 0.8187 | likely_pathogenic | 0.8424 | pathogenic | -1.447 | Destabilizing | 0.958 | D | 0.723 | prob.delet. | None | None | None | None | N |
| L/Y | 0.8418 | likely_pathogenic | 0.8623 | pathogenic | -1.189 | Destabilizing | 0.667 | D | 0.734 | prob.delet. | 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.