Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 7867 | 23824;23825;23826 | chr2:178720043;178720042;178720041 | chr2:179584770;179584769;179584768 |
| N2AB | 7550 | 22873;22874;22875 | chr2:178720043;178720042;178720041 | chr2:179584770;179584769;179584768 |
| N2A | 6623 | 20092;20093;20094 | chr2:178720043;178720042;178720041 | chr2:179584770;179584769;179584768 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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/M | rs1334032406  |
-1.16 | 0.171 | N | 0.573 | 0.054 | 0.257786959452 | 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 |
| I/M | rs1334032406 |
-1.16 | 0.171 | N | 0.573 | 0.054 | 0.257786959452 | gnomAD-4.0.0 | 2.73738E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99583E-07 | 3.47891E-05 | 0 |
| I/T | rs376689567 |
-2.242 | None | N | 0.363 | 0.078 | None | gnomAD-2.1.1 | 7.15E-06 | None | None | None | None | N | None | 8.27E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs376689567 |
-2.242 | None | N | 0.363 | 0.078 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 1.20651E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs376689567 |
-2.242 | None | N | 0.363 | 0.078 | None | gnomAD-4.0.0 | 3.28688E-05 | None | None | None | None | N | None | 1.20651E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs1446627286 |
-1.466 | None | N | 0.2 | 0.031 | 0.200317383148 | 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 |
| I/V | rs1446627286 |
-1.466 | None | N | 0.2 | 0.031 | 0.200317383148 | gnomAD-4.0.0 | 2.05301E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.31943E-05 | 1.65722E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.2404 | likely_benign | 0.2558 | benign | -2.494 | Highly Destabilizing | 0.007 | N | 0.467 | neutral | None | None | None | None | N |
| I/C | 0.6258 | likely_pathogenic | 0.6437 | pathogenic | -1.818 | Destabilizing | 0.356 | N | 0.609 | neutral | None | None | None | None | N |
| I/D | 0.6176 | likely_pathogenic | 0.6458 | pathogenic | -2.444 | Highly Destabilizing | 0.072 | N | 0.613 | neutral | None | None | None | None | N |
| I/E | 0.5522 | ambiguous | 0.5904 | pathogenic | -2.276 | Highly Destabilizing | 0.072 | N | 0.603 | neutral | None | None | None | None | N |
| I/F | 0.1274 | likely_benign | 0.1452 | benign | -1.511 | Destabilizing | 0.072 | N | 0.551 | neutral | None | None | None | None | N |
| I/G | 0.5128 | ambiguous | 0.5478 | ambiguous | -2.976 | Highly Destabilizing | 0.031 | N | 0.555 | neutral | None | None | None | None | N |
| I/H | 0.3591 | ambiguous | 0.3765 | ambiguous | -2.225 | Highly Destabilizing | 0.628 | D | 0.64 | neutral | None | None | None | None | N |
| I/K | 0.3572 | ambiguous | 0.394 | ambiguous | -1.701 | Destabilizing | 0.055 | N | 0.606 | neutral | N | 0.455611041 | None | None | N |
| I/L | 0.1157 | likely_benign | 0.1274 | benign | -1.126 | Destabilizing | 0.005 | N | 0.42 | neutral | N | 0.449858505 | None | None | N |
| I/M | 0.1121 | likely_benign | 0.1231 | benign | -1.117 | Destabilizing | 0.171 | N | 0.573 | neutral | N | 0.490147689 | None | None | N |
| I/N | 0.2024 | likely_benign | 0.2102 | benign | -1.877 | Destabilizing | 0.072 | N | 0.62 | neutral | None | None | None | None | N |
| I/P | 0.9411 | likely_pathogenic | 0.938 | pathogenic | -1.561 | Destabilizing | 0.136 | N | 0.605 | neutral | None | None | None | None | N |
| I/Q | 0.3885 | ambiguous | 0.4075 | ambiguous | -1.852 | Destabilizing | 0.356 | N | 0.643 | neutral | None | None | None | None | N |
| I/R | 0.242 | likely_benign | 0.2737 | benign | -1.316 | Destabilizing | 0.055 | N | 0.647 | neutral | N | 0.455090966 | None | None | N |
| I/S | 0.169 | likely_benign | 0.1747 | benign | -2.621 | Highly Destabilizing | 0.001 | N | 0.489 | neutral | None | None | None | None | N |
| I/T | 0.1073 | likely_benign | 0.1034 | benign | -2.32 | Highly Destabilizing | None | N | 0.363 | neutral | N | 0.329681598 | None | None | N |
| I/V | 0.0638 | likely_benign | 0.0704 | benign | -1.561 | Destabilizing | None | N | 0.2 | neutral | N | 0.411436189 | None | None | N |
| I/W | 0.7093 | likely_pathogenic | 0.7291 | pathogenic | -1.763 | Destabilizing | 0.864 | D | 0.67 | neutral | None | None | None | None | N |
| I/Y | 0.4148 | ambiguous | 0.4168 | ambiguous | -1.529 | Destabilizing | 0.356 | N | 0.605 | 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.