Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17976 | 54151;54152;54153 | chr2:178605251;178605250;178605249 | chr2:179469978;179469977;179469976 |
| N2AB | 16335 | 49228;49229;49230 | chr2:178605251;178605250;178605249 | chr2:179469978;179469977;179469976 |
| N2A | 15408 | 46447;46448;46449 | chr2:178605251;178605250;178605249 | chr2:179469978;179469977;179469976 |
| N2B | 8911 | 26956;26957;26958 | chr2:178605251;178605250;178605249 | chr2:179469978;179469977;179469976 |
| Novex-1 | 9036 | 27331;27332;27333 | chr2:178605251;178605250;178605249 | chr2:179469978;179469977;179469976 |
| Novex-2 | 9103 | 27532;27533;27534 | chr2:178605251;178605250;178605249 | chr2:179469978;179469977;179469976 |
| 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/N | rs1293562368  |
None | 0.999 | N | 0.687 | 0.657 | 0.868386450272 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/N | rs1293562368 |
None | 0.999 | N | 0.687 | 0.657 | 0.868386450272 | gnomAD-4.0.0 | 6.58189E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47223E-05 | 0 | 0 |
| I/T | rs1293562368 |
None | 0.998 | N | 0.512 | 0.573 | 0.72263772115 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs1293562368 |
None | 0.998 | N | 0.512 | 0.573 | 0.72263772115 | gnomAD-4.0.0 | 6.58189E-06 | None | None | None | None | N | None | 2.41488E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs371424482 |
-0.806 | 0.889 | N | 0.307 | 0.191 | None | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 1.14784E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs371424482 |
-0.806 | 0.889 | N | 0.307 | 0.191 | None | gnomAD-3.1.2 | 1.98E-05 | None | None | None | None | N | None | 7.25E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs371424482 |
-0.806 | 0.889 | N | 0.307 | 0.191 | None | gnomAD-4.0.0 | 8.12176E-06 | None | None | None | None | N | None | 1.39889E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.8915 | likely_pathogenic | 0.8519 | pathogenic | -2.067 | Highly Destabilizing | 0.996 | D | 0.401 | neutral | None | None | None | None | N |
| I/C | 0.9474 | likely_pathogenic | 0.9282 | pathogenic | -1.472 | Destabilizing | 1.0 | D | 0.543 | neutral | None | None | None | None | N |
| I/D | 0.9937 | likely_pathogenic | 0.9903 | pathogenic | -1.723 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | N |
| I/E | 0.9628 | likely_pathogenic | 0.9446 | pathogenic | -1.602 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | N |
| I/F | 0.4239 | ambiguous | 0.374 | ambiguous | -1.165 | Destabilizing | 0.997 | D | 0.472 | neutral | N | 0.493912444 | None | None | N |
| I/G | 0.9835 | likely_pathogenic | 0.9766 | pathogenic | -2.512 | Highly Destabilizing | 1.0 | D | 0.673 | neutral | None | None | None | None | N |
| I/H | 0.9543 | likely_pathogenic | 0.9305 | pathogenic | -1.688 | Destabilizing | 1.0 | D | 0.663 | neutral | None | None | None | None | N |
| I/K | 0.9132 | likely_pathogenic | 0.8706 | pathogenic | -1.746 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | N |
| I/L | 0.1961 | likely_benign | 0.1725 | benign | -0.851 | Destabilizing | 0.104 | N | 0.117 | neutral | N | 0.492460928 | None | None | N |
| I/M | 0.2162 | likely_benign | 0.1762 | benign | -0.76 | Destabilizing | 0.997 | D | 0.481 | neutral | D | 0.523362625 | None | None | N |
| I/N | 0.9518 | likely_pathogenic | 0.9261 | pathogenic | -1.806 | Destabilizing | 0.999 | D | 0.687 | prob.neutral | N | 0.515410514 | None | None | N |
| I/P | 0.9877 | likely_pathogenic | 0.9885 | pathogenic | -1.229 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| I/Q | 0.9142 | likely_pathogenic | 0.8717 | pathogenic | -1.807 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | N |
| I/R | 0.8838 | likely_pathogenic | 0.8315 | pathogenic | -1.255 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | N |
| I/S | 0.9432 | likely_pathogenic | 0.9136 | pathogenic | -2.498 | Highly Destabilizing | 0.999 | D | 0.574 | neutral | N | 0.496292301 | None | None | N |
| I/T | 0.8951 | likely_pathogenic | 0.8415 | pathogenic | -2.241 | Highly Destabilizing | 0.998 | D | 0.512 | neutral | N | 0.487391531 | None | None | N |
| I/V | 0.1089 | likely_benign | 0.0995 | benign | -1.229 | Destabilizing | 0.889 | D | 0.307 | neutral | N | 0.478835483 | None | None | N |
| I/W | 0.9426 | likely_pathogenic | 0.9283 | pathogenic | -1.362 | Destabilizing | 1.0 | D | 0.662 | neutral | None | None | None | None | N |
| I/Y | 0.8718 | likely_pathogenic | 0.8363 | pathogenic | -1.125 | Destabilizing | 1.0 | D | 0.575 | 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.