Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3415 | 10468;10469;10470 | chr2:178759044;178759043;178759042 | chr2:179623771;179623770;179623769 |
| N2AB | 3415 | 10468;10469;10470 | chr2:178759044;178759043;178759042 | chr2:179623771;179623770;179623769 |
| N2A | 3415 | 10468;10469;10470 | chr2:178759044;178759043;178759042 | chr2:179623771;179623770;179623769 |
| N2B | 3369 | 10330;10331;10332 | chr2:178759044;178759043;178759042 | chr2:179623771;179623770;179623769 |
| Novex-1 | 3369 | 10330;10331;10332 | chr2:178759044;178759043;178759042 | chr2:179623771;179623770;179623769 |
| Novex-2 | 3369 | 10330;10331;10332 | chr2:178759044;178759043;178759042 | chr2:179623771;179623770;179623769 |
| Novex-3 | 3415 | 10468;10469;10470 | chr2:178759044;178759043;178759042 | chr2:179623771;179623770;179623769 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/M | rs761799688  |
-1.036 | 0.977 | D | 0.728 | 0.496 | 0.819533414578 | gnomAD-2.1.1 | 1.55333E-04 | None | None | None | None | N | None | 6.15E-05 | 1.09896E-03 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/M | rs761799688 |
-1.036 | 0.977 | D | 0.728 | 0.496 | 0.819533414578 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 1.96721E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/M | rs761799688 |
-1.036 | 0.977 | D | 0.728 | 0.496 | 0.819533414578 | gnomAD-4.0.0 | 2.91229E-05 | None | None | None | None | N | None | 1.33497E-05 | 6.3365E-04 | None | 0 | 0 | None | 0 | 0 | 3.39003E-06 | 0 | 6.40205E-05 |
| T/S | rs1488856141 |
-1.154 | 0.011 | N | 0.466 | 0.249 | 0.21737058555 | gnomAD-2.1.1 | 7.97E-06 | None | None | None | None | N | None | 0 | 5.78E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/S | rs1488856141 |
-1.154 | 0.011 | N | 0.466 | 0.249 | 0.21737058555 | gnomAD-4.0.0 | 3.18149E-06 | None | None | None | None | N | None | 0 | 4.57289E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1237 | likely_benign | 0.103 | benign | -1.373 | Destabilizing | 0.001 | N | 0.373 | neutral | D | 0.556939718 | None | None | N |
| T/C | 0.5681 | likely_pathogenic | 0.4729 | ambiguous | -0.643 | Destabilizing | 0.909 | D | 0.717 | prob.delet. | None | None | None | None | N |
| T/D | 0.6793 | likely_pathogenic | 0.6761 | pathogenic | -0.692 | Destabilizing | 0.567 | D | 0.709 | prob.delet. | None | None | None | None | N |
| T/E | 0.4879 | ambiguous | 0.532 | ambiguous | -0.471 | Destabilizing | 0.272 | N | 0.696 | prob.neutral | None | None | None | None | N |
| T/F | 0.3802 | ambiguous | 0.3637 | ambiguous | -1.159 | Destabilizing | 0.726 | D | 0.764 | deleterious | None | None | None | None | N |
| T/G | 0.4701 | ambiguous | 0.415 | ambiguous | -1.769 | Destabilizing | 0.157 | N | 0.697 | prob.neutral | None | None | None | None | N |
| T/H | 0.2678 | likely_benign | 0.2907 | benign | -1.592 | Destabilizing | 0.968 | D | 0.749 | deleterious | None | None | None | None | N |
| T/I | 0.2048 | likely_benign | 0.2195 | benign | -0.314 | Destabilizing | 0.567 | D | 0.721 | prob.delet. | None | None | None | None | N |
| T/K | 0.2973 | likely_benign | 0.3332 | benign | 0.181 | Stabilizing | 0.01 | N | 0.525 | neutral | N | 0.50217237 | None | None | N |
| T/L | 0.1537 | likely_benign | 0.1647 | benign | -0.314 | Destabilizing | 0.157 | N | 0.675 | neutral | None | None | None | None | N |
| T/M | 0.1359 | likely_benign | 0.1437 | benign | -0.406 | Destabilizing | 0.977 | D | 0.728 | prob.delet. | D | 0.580714362 | None | None | N |
| T/N | 0.227 | likely_benign | 0.2278 | benign | -0.451 | Destabilizing | 0.567 | D | 0.633 | neutral | None | None | None | None | N |
| T/P | 0.8675 | likely_pathogenic | 0.8554 | pathogenic | -0.64 | Destabilizing | 0.497 | N | 0.719 | prob.delet. | D | 0.721136152 | None | None | N |
| T/Q | 0.2761 | likely_benign | 0.3095 | benign | -0.255 | Destabilizing | 0.567 | D | 0.738 | prob.delet. | None | None | None | None | N |
| T/R | 0.1932 | likely_benign | 0.2123 | benign | -0.094 | Destabilizing | 0.557 | D | 0.727 | prob.delet. | N | 0.517101612 | None | None | N |
| T/S | 0.147 | likely_benign | 0.1309 | benign | -0.89 | Destabilizing | 0.011 | N | 0.466 | neutral | N | 0.493146758 | None | None | N |
| T/V | 0.1809 | likely_benign | 0.1781 | benign | -0.64 | Destabilizing | 0.157 | N | 0.609 | neutral | None | None | None | None | N |
| T/W | 0.7915 | likely_pathogenic | 0.7713 | pathogenic | -1.108 | Destabilizing | 0.968 | D | 0.76 | deleterious | None | None | None | None | N |
| T/Y | 0.3992 | ambiguous | 0.4061 | ambiguous | -0.756 | Destabilizing | 0.726 | D | 0.77 | 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.