Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16446 | 49561;49562;49563 | chr2:178614061;178614060;178614059 | chr2:179478788;179478787;179478786 |
| N2AB | 14805 | 44638;44639;44640 | chr2:178614061;178614060;178614059 | chr2:179478788;179478787;179478786 |
| N2A | 13878 | 41857;41858;41859 | chr2:178614061;178614060;178614059 | chr2:179478788;179478787;179478786 |
| N2B | 7381 | 22366;22367;22368 | chr2:178614061;178614060;178614059 | chr2:179478788;179478787;179478786 |
| Novex-1 | 7506 | 22741;22742;22743 | chr2:178614061;178614060;178614059 | chr2:179478788;179478787;179478786 |
| Novex-2 | 7573 | 22942;22943;22944 | chr2:178614061;178614060;178614059 | chr2:179478788;179478787;179478786 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs2056847941  |
None | 0.95 | N | 0.733 | 0.316 | 0.149567049428 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07641E-04 | 0 |
| Y/C | rs2056847941 |
None | 0.95 | N | 0.733 | 0.316 | 0.149567049428 | gnomAD-4.0.0 | 2.03051E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.20506E-06 | 4.70013E-05 | 0 |
| Y/H | rs774443816 |
0.689 | 0.623 | N | 0.573 | 0.258 | 0.31077124679 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | I | None | 0 | 2.92E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| Y/H | rs774443816 |
0.689 | 0.623 | N | 0.573 | 0.258 | 0.31077124679 | gnomAD-4.0.0 | 1.36998E-06 | None | None | None | None | I | None | 0 | 2.24346E-05 | None | 0 | 0 | None | 0 | 0 | 8.99951E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.9009 | likely_pathogenic | 0.8545 | pathogenic | -0.762 | Destabilizing | 0.236 | N | 0.465 | neutral | None | None | None | None | I |
| Y/C | 0.5701 | likely_pathogenic | 0.4981 | ambiguous | 0.058 | Stabilizing | 0.95 | D | 0.733 | deleterious | N | 0.462071694 | None | None | I |
| Y/D | 0.739 | likely_pathogenic | 0.6613 | pathogenic | 0.965 | Stabilizing | 0.834 | D | 0.711 | prob.delet. | N | 0.450868781 | None | None | I |
| Y/E | 0.9481 | likely_pathogenic | 0.9292 | pathogenic | 0.952 | Stabilizing | 0.687 | D | 0.68 | prob.neutral | None | None | None | None | I |
| Y/F | 0.1441 | likely_benign | 0.1457 | benign | -0.362 | Destabilizing | 0.001 | N | 0.427 | neutral | D | 0.543853178 | None | None | I |
| Y/G | 0.872 | likely_pathogenic | 0.8244 | pathogenic | -0.956 | Destabilizing | 0.687 | D | 0.687 | prob.delet. | None | None | None | None | I |
| Y/H | 0.4907 | ambiguous | 0.4094 | ambiguous | 0.154 | Stabilizing | 0.623 | D | 0.573 | neutral | N | 0.468732841 | None | None | I |
| Y/I | 0.8788 | likely_pathogenic | 0.8594 | pathogenic | -0.271 | Destabilizing | 0.351 | N | 0.603 | neutral | None | None | None | None | I |
| Y/K | 0.955 | likely_pathogenic | 0.9404 | pathogenic | 0.131 | Stabilizing | 0.687 | D | 0.673 | prob.neutral | None | None | None | None | I |
| Y/L | 0.7787 | likely_pathogenic | 0.7441 | pathogenic | -0.271 | Destabilizing | 0.134 | N | 0.665 | prob.neutral | None | None | None | None | I |
| Y/M | 0.8771 | likely_pathogenic | 0.8542 | pathogenic | -0.096 | Destabilizing | 0.892 | D | 0.549 | neutral | None | None | None | None | I |
| Y/N | 0.4338 | ambiguous | 0.4102 | ambiguous | -0.065 | Destabilizing | 0.834 | D | 0.657 | prob.neutral | N | 0.462053529 | None | None | I |
| Y/P | 0.9362 | likely_pathogenic | 0.894 | pathogenic | -0.415 | Destabilizing | 0.87 | D | 0.695 | prob.delet. | None | None | None | None | I |
| Y/Q | 0.9216 | likely_pathogenic | 0.8918 | pathogenic | -0.009 | Destabilizing | 0.87 | D | 0.56 | neutral | None | None | None | None | I |
| Y/R | 0.9234 | likely_pathogenic | 0.9003 | pathogenic | 0.393 | Stabilizing | 0.687 | D | 0.653 | prob.neutral | None | None | None | None | I |
| Y/S | 0.6628 | likely_pathogenic | 0.5604 | ambiguous | -0.529 | Destabilizing | 0.623 | D | 0.651 | prob.neutral | N | 0.462479283 | None | None | I |
| Y/T | 0.895 | likely_pathogenic | 0.8503 | pathogenic | -0.451 | Destabilizing | 0.687 | D | 0.675 | prob.neutral | None | None | None | None | I |
| Y/V | 0.8415 | likely_pathogenic | 0.8092 | pathogenic | -0.415 | Destabilizing | 0.134 | N | 0.629 | neutral | None | None | None | None | I |
| Y/W | 0.6489 | likely_pathogenic | 0.603 | pathogenic | -0.46 | Destabilizing | 0.892 | D | 0.562 | 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.