Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14812 | 44659;44660;44661 | chr2:178625387;178625386;178625385 | chr2:179490114;179490113;179490112 |
| N2AB | 13171 | 39736;39737;39738 | chr2:178625387;178625386;178625385 | chr2:179490114;179490113;179490112 |
| N2A | 12244 | 36955;36956;36957 | chr2:178625387;178625386;178625385 | chr2:179490114;179490113;179490112 |
| N2B | 5747 | 17464;17465;17466 | chr2:178625387;178625386;178625385 | chr2:179490114;179490113;179490112 |
| Novex-1 | 5872 | 17839;17840;17841 | chr2:178625387;178625386;178625385 | chr2:179490114;179490113;179490112 |
| Novex-2 | 5939 | 18040;18041;18042 | chr2:178625387;178625386;178625385 | chr2:179490114;179490113;179490112 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs745698096  |
-0.196 | 1.0 | D | 0.688 | 0.473 | 0.763848737128 | gnomAD-2.1.1 | 4.69E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.84E-06 | 0 |
| R/C | rs745698096 |
-0.196 | 1.0 | D | 0.688 | 0.473 | 0.763848737128 | gnomAD-4.0.0 | 3.51418E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.8226E-06 | 3.84724E-05 | 0 |
| R/H | rs375574483 |
-0.938 | 1.0 | N | 0.611 | 0.376 | None | gnomAD-2.1.1 | 4.5E-05 | None | None | None | None | N | None | 4.59E-05 | 0 | None | 0 | 1.84525E-04 | None | 0 | None | 0 | 5.15E-05 | 1.65125E-04 |
| R/H | rs375574483 |
-0.938 | 1.0 | N | 0.611 | 0.376 | None | gnomAD-3.1.2 | 3.3E-05 | None | None | None | None | N | None | 4.84E-05 | 6.58E-05 | 0 | 0 | 0 | None | 0 | 0 | 2.95E-05 | 0 | 0 |
| R/H | rs375574483 |
-0.938 | 1.0 | N | 0.611 | 0.376 | None | gnomAD-4.0.0 | 4.19527E-05 | None | None | None | None | N | None | 6.92828E-05 | 1.91872E-05 | None | 0 | 9.41664E-05 | None | 0 | 0 | 4.5513E-05 | 1.21051E-05 | 3.28526E-05 |
| R/S | rs745698096 |
-0.253 | 0.996 | N | 0.635 | 0.377 | 0.455081427078 | gnomAD-2.1.1 | 4.69E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 6.71E-05 | None | 0 | None | 0 | 0 | 0 |
| R/S | rs745698096 |
-0.253 | 0.996 | N | 0.635 | 0.377 | 0.455081427078 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 3.89257E-04 | None | 0 | 0 | 0 | 0 | 0 |
| R/S | rs745698096 |
-0.253 | 0.996 | N | 0.635 | 0.377 | 0.455081427078 | gnomAD-4.0.0 | 1.14326E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 4.21506E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.4179 | ambiguous | 0.461 | ambiguous | -0.087 | Destabilizing | 0.992 | D | 0.583 | neutral | None | None | None | None | N |
| R/C | 0.1825 | likely_benign | 0.2148 | benign | -0.111 | Destabilizing | 1.0 | D | 0.688 | prob.neutral | D | 0.577836826 | None | None | N |
| R/D | 0.719 | likely_pathogenic | 0.7749 | pathogenic | 0.037 | Stabilizing | 0.999 | D | 0.682 | prob.neutral | None | None | None | None | N |
| R/E | 0.4259 | ambiguous | 0.482 | ambiguous | 0.106 | Stabilizing | 0.992 | D | 0.533 | neutral | None | None | None | None | N |
| R/F | 0.4596 | ambiguous | 0.5209 | ambiguous | -0.276 | Destabilizing | 1.0 | D | 0.688 | prob.neutral | None | None | None | None | N |
| R/G | 0.3074 | likely_benign | 0.3595 | ambiguous | -0.303 | Destabilizing | 0.998 | D | 0.602 | neutral | D | 0.551394562 | None | None | N |
| R/H | 0.0945 | likely_benign | 0.1072 | benign | -0.808 | Destabilizing | 1.0 | D | 0.611 | neutral | N | 0.495908571 | None | None | N |
| R/I | 0.2242 | likely_benign | 0.2698 | benign | 0.45 | Stabilizing | 1.0 | D | 0.712 | prob.delet. | None | None | None | None | N |
| R/K | 0.1146 | likely_benign | 0.1287 | benign | -0.071 | Destabilizing | 0.611 | D | 0.229 | neutral | None | None | None | None | N |
| R/L | 0.2445 | likely_benign | 0.2803 | benign | 0.45 | Stabilizing | 0.998 | D | 0.602 | neutral | N | 0.509837177 | None | None | N |
| R/M | 0.3048 | likely_benign | 0.3682 | ambiguous | 0.093 | Stabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | N |
| R/N | 0.5895 | likely_pathogenic | 0.6693 | pathogenic | 0.286 | Stabilizing | 0.999 | D | 0.601 | neutral | None | None | None | None | N |
| R/P | 0.9076 | likely_pathogenic | 0.9116 | pathogenic | 0.292 | Stabilizing | 1.0 | D | 0.701 | prob.neutral | D | 0.618071929 | None | None | N |
| R/Q | 0.1141 | likely_benign | 0.132 | benign | 0.133 | Stabilizing | 0.998 | D | 0.605 | neutral | None | None | None | None | N |
| R/S | 0.4785 | ambiguous | 0.5469 | ambiguous | -0.167 | Destabilizing | 0.996 | D | 0.635 | neutral | N | 0.470761114 | None | None | N |
| R/T | 0.2632 | likely_benign | 0.3165 | benign | 0.044 | Stabilizing | 0.999 | D | 0.657 | neutral | None | None | None | None | N |
| R/V | 0.2993 | likely_benign | 0.3355 | benign | 0.292 | Stabilizing | 0.999 | D | 0.704 | prob.neutral | None | None | None | None | N |
| R/W | 0.1842 | likely_benign | 0.2219 | benign | -0.253 | Destabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | N |
| R/Y | 0.3505 | ambiguous | 0.4208 | ambiguous | 0.15 | Stabilizing | 1.0 | D | 0.7 | prob.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.