Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1475 | 4648;4649;4650 | chr2:178777761;178777760;178777759 | chr2:179642488;179642487;179642486 |
| N2AB | 1475 | 4648;4649;4650 | chr2:178777761;178777760;178777759 | chr2:179642488;179642487;179642486 |
| N2A | 1475 | 4648;4649;4650 | chr2:178777761;178777760;178777759 | chr2:179642488;179642487;179642486 |
| N2B | 1429 | 4510;4511;4512 | chr2:178777761;178777760;178777759 | chr2:179642488;179642487;179642486 |
| Novex-1 | 1429 | 4510;4511;4512 | chr2:178777761;178777760;178777759 | chr2:179642488;179642487;179642486 |
| Novex-2 | 1429 | 4510;4511;4512 | chr2:178777761;178777760;178777759 | chr2:179642488;179642487;179642486 |
| Novex-3 | 1475 | 4648;4649;4650 | chr2:178777761;178777760;178777759 | chr2:179642488;179642487;179642486 |
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/K | rs374591242  |
0.081 | 0.997 | N | 0.511 | 0.401 | None | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.82E-06 | 0 |
| R/K | rs374591242 |
0.081 | 0.997 | N | 0.511 | 0.401 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| R/K | rs374591242 |
0.081 | 0.997 | N | 0.511 | 0.401 | None | gnomAD-4.0.0 | 5.12262E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.56791E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9717 | likely_pathogenic | 0.9772 | pathogenic | -0.759 | Destabilizing | 0.999 | D | 0.601 | neutral | None | None | None | None | I |
| R/C | 0.7331 | likely_pathogenic | 0.7611 | pathogenic | -0.757 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | I |
| R/D | 0.9948 | likely_pathogenic | 0.9958 | pathogenic | 0.101 | Stabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | I |
| R/E | 0.9574 | likely_pathogenic | 0.9664 | pathogenic | 0.232 | Stabilizing | 0.999 | D | 0.624 | neutral | None | None | None | None | I |
| R/F | 0.9793 | likely_pathogenic | 0.9859 | pathogenic | -0.661 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | I |
| R/G | 0.961 | likely_pathogenic | 0.968 | pathogenic | -1.053 | Destabilizing | 1.0 | D | 0.65 | neutral | D | 0.689403456 | None | None | I |
| R/H | 0.5612 | ambiguous | 0.6098 | pathogenic | -1.411 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | I |
| R/I | 0.9015 | likely_pathogenic | 0.9216 | pathogenic | 0.024 | Stabilizing | 1.0 | D | 0.725 | prob.delet. | N | 0.507460364 | None | None | I |
| R/K | 0.5915 | likely_pathogenic | 0.6363 | pathogenic | -0.584 | Destabilizing | 0.997 | D | 0.511 | neutral | N | 0.510185842 | None | None | I |
| R/L | 0.8935 | likely_pathogenic | 0.9138 | pathogenic | 0.024 | Stabilizing | 1.0 | D | 0.65 | neutral | None | None | None | None | I |
| R/M | 0.957 | likely_pathogenic | 0.9666 | pathogenic | -0.386 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | I |
| R/N | 0.9852 | likely_pathogenic | 0.9888 | pathogenic | -0.212 | Destabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | I |
| R/P | 0.9962 | likely_pathogenic | 0.9967 | pathogenic | -0.217 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | I |
| R/Q | 0.6147 | likely_pathogenic | 0.6535 | pathogenic | -0.329 | Destabilizing | 1.0 | D | 0.732 | prob.delet. | None | None | None | None | I |
| R/S | 0.9704 | likely_pathogenic | 0.9761 | pathogenic | -0.98 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | N | 0.509274679 | None | None | I |
| R/T | 0.9441 | likely_pathogenic | 0.9496 | pathogenic | -0.66 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | N | 0.500555274 | None | None | I |
| R/V | 0.9135 | likely_pathogenic | 0.9298 | pathogenic | -0.217 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | I |
| R/W | 0.8358 | likely_pathogenic | 0.8753 | pathogenic | -0.381 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | I |
| R/Y | 0.9461 | likely_pathogenic | 0.9621 | pathogenic | -0.074 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | 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.