Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 5041 | 15346;15347;15348 | chr2:178734803;178734802;178734801 | chr2:179599530;179599529;179599528 |
| N2AB | 4724 | 14395;14396;14397 | chr2:178734803;178734802;178734801 | chr2:179599530;179599529;179599528 |
| N2A | 3797 | 11614;11615;11616 | chr2:178734803;178734802;178734801 | chr2:179599530;179599529;179599528 |
| 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/S | rs752780850  |
-2.887 | 0.667 | D | 0.859 | 0.752 | None | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| I/S | rs752780850 |
-2.887 | 0.667 | D | 0.859 | 0.752 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/S | rs752780850 |
-2.887 | 0.667 | D | 0.859 | 0.752 | None | gnomAD-4.0.0 | 8.96728E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.67514E-05 | 0 | 0 |
| I/V | rs760814989 |
-1.51 | 0.001 | D | 0.268 | 0.252 | 0.565612946506 | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.05086E-04 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs760814989 |
-1.51 | 0.001 | D | 0.268 | 0.252 | 0.565612946506 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.92678E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs760814989 |
-1.51 | 0.001 | D | 0.268 | 0.252 | 0.565612946506 | gnomAD-4.0.0 | 4.95745E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.33708E-04 | None | 0 | 0 | 8.47614E-07 | 0 | 1.60113E-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 | 0.8592 | likely_pathogenic | 0.8386 | pathogenic | -2.544 | Highly Destabilizing | 0.157 | N | 0.729 | prob.delet. | None | None | None | None | N |
| I/C | 0.8836 | likely_pathogenic | 0.8878 | pathogenic | -2.23 | Highly Destabilizing | 0.968 | D | 0.769 | deleterious | None | None | None | None | N |
| I/D | 0.9873 | likely_pathogenic | 0.9866 | pathogenic | -2.485 | Highly Destabilizing | 0.89 | D | 0.893 | deleterious | None | None | None | None | N |
| I/E | 0.9754 | likely_pathogenic | 0.9713 | pathogenic | -2.364 | Highly Destabilizing | 0.726 | D | 0.893 | deleterious | None | None | None | None | N |
| I/F | 0.2033 | likely_benign | 0.1897 | benign | -1.753 | Destabilizing | 0.331 | N | 0.739 | prob.delet. | D | 0.573743659 | None | None | N |
| I/G | 0.9733 | likely_pathogenic | 0.9697 | pathogenic | -3.015 | Highly Destabilizing | 0.726 | D | 0.889 | deleterious | None | None | None | None | N |
| I/H | 0.9228 | likely_pathogenic | 0.9149 | pathogenic | -2.258 | Highly Destabilizing | 0.968 | D | 0.877 | deleterious | None | None | None | None | N |
| I/K | 0.9198 | likely_pathogenic | 0.9088 | pathogenic | -1.989 | Destabilizing | 0.726 | D | 0.893 | deleterious | None | None | None | None | N |
| I/L | 0.1139 | likely_benign | 0.1204 | benign | -1.232 | Destabilizing | None | N | 0.295 | neutral | D | 0.534709264 | None | None | N |
| I/M | 0.1071 | likely_benign | 0.1083 | benign | -1.215 | Destabilizing | 0.331 | N | 0.712 | prob.delet. | D | 0.617299058 | None | None | N |
| I/N | 0.8855 | likely_pathogenic | 0.8764 | pathogenic | -2.09 | Highly Destabilizing | 0.859 | D | 0.878 | deleterious | D | 0.743470403 | None | None | N |
| I/P | 0.993 | likely_pathogenic | 0.9939 | pathogenic | -1.645 | Destabilizing | 0.89 | D | 0.889 | deleterious | None | None | None | None | N |
| I/Q | 0.9354 | likely_pathogenic | 0.9273 | pathogenic | -2.14 | Highly Destabilizing | 0.89 | D | 0.897 | deleterious | None | None | None | None | N |
| I/R | 0.889 | likely_pathogenic | 0.8743 | pathogenic | -1.46 | Destabilizing | 0.726 | D | 0.878 | deleterious | None | None | None | None | N |
| I/S | 0.8877 | likely_pathogenic | 0.8765 | pathogenic | -2.84 | Highly Destabilizing | 0.667 | D | 0.859 | deleterious | D | 0.779743562 | None | None | N |
| I/T | 0.8328 | likely_pathogenic | 0.8168 | pathogenic | -2.573 | Highly Destabilizing | 0.22 | N | 0.785 | deleterious | D | 0.779948151 | None | None | N |
| I/V | 0.1126 | likely_benign | 0.1079 | benign | -1.645 | Destabilizing | 0.001 | N | 0.268 | neutral | D | 0.540094205 | None | None | N |
| I/W | 0.8841 | likely_pathogenic | 0.8762 | pathogenic | -1.927 | Destabilizing | 0.968 | D | 0.875 | deleterious | None | None | None | None | N |
| I/Y | 0.7411 | likely_pathogenic | 0.7481 | pathogenic | -1.709 | Destabilizing | 0.726 | D | 0.778 | deleterious | 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.