Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18221 | 54886;54887;54888 | chr2:178604026;178604025;178604024 | chr2:179468753;179468752;179468751 |
| N2AB | 16580 | 49963;49964;49965 | chr2:178604026;178604025;178604024 | chr2:179468753;179468752;179468751 |
| N2A | 15653 | 47182;47183;47184 | chr2:178604026;178604025;178604024 | chr2:179468753;179468752;179468751 |
| N2B | 9156 | 27691;27692;27693 | chr2:178604026;178604025;178604024 | chr2:179468753;179468752;179468751 |
| Novex-1 | 9281 | 28066;28067;28068 | chr2:178604026;178604025;178604024 | chr2:179468753;179468752;179468751 |
| Novex-2 | 9348 | 28267;28268;28269 | chr2:178604026;178604025;178604024 | chr2:179468753;179468752;179468751 |
| 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/L | rs375091820  |
-0.381 | 0.136 | N | 0.473 | 0.059 | 0.227260227426 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| I/L | rs375091820 |
-0.381 | 0.136 | N | 0.473 | 0.059 | 0.227260227426 | gnomAD-4.0.0 | 6.8451E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.16007E-05 | 0 |
| I/T | rs1418665991 |
-2.165 | 0.801 | N | 0.628 | 0.287 | 0.63963811802 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| I/T | rs1418665991 |
-2.165 | 0.801 | N | 0.628 | 0.287 | 0.63963811802 | gnomAD-4.0.0 | 1.59294E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43386E-05 | 0 |
| I/V | rs375091820 |
-0.972 | 0.002 | N | 0.231 | 0.075 | None | gnomAD-2.1.1 | 2.14E-05 | None | None | None | None | N | None | 0 | 8.48E-05 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 7.82E-06 | 1.40292E-04 |
| I/V | rs375091820 |
-0.972 | 0.002 | N | 0.231 | 0.075 | None | gnomAD-4.0.0 | 1.57437E-05 | None | None | None | None | N | None | 0 | 6.70991E-05 | None | 0 | 2.52016E-05 | None | 0 | 0 | 1.16979E-05 | 6.9604E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.7748 | likely_pathogenic | 0.7382 | pathogenic | -1.661 | Destabilizing | 0.525 | D | 0.552 | neutral | None | None | None | None | N |
| I/C | 0.8306 | likely_pathogenic | 0.8333 | pathogenic | -0.614 | Destabilizing | 0.998 | D | 0.685 | prob.neutral | None | None | None | None | N |
| I/D | 0.9802 | likely_pathogenic | 0.981 | pathogenic | -2.172 | Highly Destabilizing | 0.991 | D | 0.759 | deleterious | None | None | None | None | N |
| I/E | 0.9423 | likely_pathogenic | 0.9474 | pathogenic | -1.868 | Destabilizing | 0.974 | D | 0.753 | deleterious | None | None | None | None | N |
| I/F | 0.5194 | ambiguous | 0.4518 | ambiguous | -0.927 | Destabilizing | 0.949 | D | 0.642 | neutral | None | None | None | None | N |
| I/G | 0.9467 | likely_pathogenic | 0.9432 | pathogenic | -2.227 | Highly Destabilizing | 0.915 | D | 0.741 | deleterious | None | None | None | None | N |
| I/H | 0.9423 | likely_pathogenic | 0.943 | pathogenic | -2.088 | Highly Destabilizing | 0.998 | D | 0.74 | deleterious | None | None | None | None | N |
| I/K | 0.9398 | likely_pathogenic | 0.9411 | pathogenic | -0.935 | Destabilizing | 0.966 | D | 0.755 | deleterious | N | 0.493557007 | None | None | N |
| I/L | 0.2268 | likely_benign | 0.1707 | benign | 0.013 | Stabilizing | 0.136 | N | 0.473 | neutral | N | 0.458113494 | None | None | N |
| I/M | 0.2662 | likely_benign | 0.2195 | benign | -0.051 | Destabilizing | 0.966 | D | 0.633 | neutral | N | 0.493557007 | None | None | N |
| I/N | 0.8363 | likely_pathogenic | 0.8477 | pathogenic | -1.566 | Destabilizing | 0.991 | D | 0.761 | deleterious | None | None | None | None | N |
| I/P | 0.9551 | likely_pathogenic | 0.9516 | pathogenic | -0.532 | Destabilizing | 0.991 | D | 0.767 | deleterious | None | None | None | None | N |
| I/Q | 0.8925 | likely_pathogenic | 0.8994 | pathogenic | -1.199 | Destabilizing | 0.991 | D | 0.765 | deleterious | None | None | None | None | N |
| I/R | 0.9124 | likely_pathogenic | 0.9121 | pathogenic | -1.268 | Destabilizing | 0.966 | D | 0.762 | deleterious | N | 0.498752183 | None | None | N |
| I/S | 0.8473 | likely_pathogenic | 0.8421 | pathogenic | -2.093 | Highly Destabilizing | 0.915 | D | 0.692 | prob.neutral | None | None | None | None | N |
| I/T | 0.7791 | likely_pathogenic | 0.7952 | pathogenic | -1.625 | Destabilizing | 0.801 | D | 0.628 | neutral | N | 0.4632341 | None | None | N |
| I/V | 0.0701 | likely_benign | 0.0679 | benign | -0.532 | Destabilizing | 0.002 | N | 0.231 | neutral | N | 0.364491257 | None | None | N |
| I/W | 0.9686 | likely_pathogenic | 0.9575 | pathogenic | -1.334 | Destabilizing | 0.998 | D | 0.757 | deleterious | None | None | None | None | N |
| I/Y | 0.8881 | likely_pathogenic | 0.8777 | pathogenic | -0.955 | Destabilizing | 0.974 | D | 0.715 | 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.