Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 6288 | 19087;19088;19089 | chr2:178729294;178729293;178729292 | chr2:179594021;179594020;179594019 |
| N2AB | 5971 | 18136;18137;18138 | chr2:178729294;178729293;178729292 | chr2:179594021;179594020;179594019 |
| N2A | 5044 | 15355;15356;15357 | chr2:178729294;178729293;178729292 | chr2:179594021;179594020;179594019 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/Q | rs1381105393  |
-0.313 | 1.0 | N | 0.71 | 0.458 | 0.679835815318 | gnomAD-2.1.1 | 4.25E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.26E-06 | 0 |
| L/Q | rs1381105393 |
-0.313 | 1.0 | N | 0.71 | 0.458 | 0.679835815318 | gnomAD-4.0.0 | 3.30111E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.92582E-06 | 0 | 0 |
| L/V | rs745682900 |
-0.241 | 0.962 | N | 0.565 | 0.146 | 0.17948927462 | gnomAD-2.1.1 | 4.21E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.59E-05 | None | 0 | 0 | 0 |
| L/V | rs745682900 |
-0.241 | 0.962 | N | 0.565 | 0.146 | 0.17948927462 | gnomAD-4.0.0 | 1.64361E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.48965E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.4441 | ambiguous | 0.4243 | ambiguous | -1.663 | Destabilizing | 0.994 | D | 0.621 | neutral | None | None | None | None | I |
| L/C | 0.6783 | likely_pathogenic | 0.6156 | pathogenic | -0.891 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | I |
| L/D | 0.9119 | likely_pathogenic | 0.9166 | pathogenic | -1.085 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | I |
| L/E | 0.5899 | likely_pathogenic | 0.5942 | pathogenic | -1.088 | Destabilizing | 1.0 | D | 0.74 | deleterious | None | None | None | None | I |
| L/F | 0.197 | likely_benign | 0.1833 | benign | -1.153 | Destabilizing | 0.999 | D | 0.672 | neutral | None | None | None | None | I |
| L/G | 0.762 | likely_pathogenic | 0.7399 | pathogenic | -1.987 | Destabilizing | 1.0 | D | 0.72 | prob.delet. | None | None | None | None | I |
| L/H | 0.5174 | ambiguous | 0.4919 | ambiguous | -1.227 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | I |
| L/I | 0.1031 | likely_benign | 0.1009 | benign | -0.846 | Destabilizing | 0.683 | D | 0.272 | neutral | None | None | None | None | I |
| L/K | 0.5492 | ambiguous | 0.5344 | ambiguous | -1.185 | Destabilizing | 1.0 | D | 0.692 | prob.neutral | None | None | None | None | I |
| L/M | 0.1138 | likely_benign | 0.1072 | benign | -0.606 | Destabilizing | 0.999 | D | 0.669 | neutral | N | 0.47741722 | None | None | I |
| L/N | 0.6925 | likely_pathogenic | 0.6852 | pathogenic | -0.914 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | I |
| L/P | 0.5844 | likely_pathogenic | 0.5903 | pathogenic | -1.088 | Destabilizing | 1.0 | D | 0.745 | deleterious | N | 0.47767071 | None | None | I |
| L/Q | 0.2867 | likely_benign | 0.2659 | benign | -1.098 | Destabilizing | 1.0 | D | 0.71 | prob.delet. | N | 0.47767071 | None | None | I |
| L/R | 0.4543 | ambiguous | 0.4282 | ambiguous | -0.581 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | N | 0.47767071 | None | None | I |
| L/S | 0.5177 | ambiguous | 0.5054 | ambiguous | -1.51 | Destabilizing | 1.0 | D | 0.698 | prob.neutral | None | None | None | None | I |
| L/T | 0.4116 | ambiguous | 0.3946 | ambiguous | -1.401 | Destabilizing | 0.999 | D | 0.65 | neutral | None | None | None | None | I |
| L/V | 0.1021 | likely_benign | 0.1002 | benign | -1.088 | Destabilizing | 0.962 | D | 0.565 | neutral | N | 0.402735696 | None | None | I |
| L/W | 0.413 | ambiguous | 0.3848 | ambiguous | -1.223 | Destabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | I |
| L/Y | 0.5422 | ambiguous | 0.528 | ambiguous | -1.025 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | 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.