Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 9583 | 28972;28973;28974 | chr2:178709572;178709571;178709570 | chr2:179574299;179574298;179574297 |
| N2AB | 9266 | 28021;28022;28023 | chr2:178709572;178709571;178709570 | chr2:179574299;179574298;179574297 |
| N2A | 8339 | 25240;25241;25242 | chr2:178709572;178709571;178709570 | chr2:179574299;179574298;179574297 |
| 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/F | None | None | 0.864 | None | 0.569 | 0.274 | 0.520749599713 | gnomAD-4.0.0 | 6.89341E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.0689E-07 | 0 | 0 |
| I/L | None | None | 0.141 | None | 0.331 | 0.117 | 0.387850303812 | gnomAD-4.0.0 | 6.89341E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.16352E-05 | 0 |
| I/M | rs1219437440  |
-0.837 | 0.864 | None | 0.559 | 0.274 | 0.508398094826 | gnomAD-2.1.1 | 3.18E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| I/M | rs1219437440 |
-0.837 | 0.864 | None | 0.559 | 0.274 | 0.508398094826 | 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/M | rs1219437440 |
-0.837 | 0.864 | None | 0.559 | 0.274 | 0.508398094826 | gnomAD-4.0.0 | 6.56953E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.46977E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9514 | likely_pathogenic | 0.9288 | pathogenic | -2.321 | Highly Destabilizing | 0.547 | D | 0.456 | neutral | None | None | None | None | N |
| I/C | 0.9674 | likely_pathogenic | 0.9593 | pathogenic | -1.834 | Destabilizing | 0.985 | D | 0.583 | neutral | None | None | None | None | N |
| I/D | 0.9977 | likely_pathogenic | 0.9965 | pathogenic | -2.909 | Highly Destabilizing | 0.945 | D | 0.673 | neutral | None | None | None | None | N |
| I/E | 0.9921 | likely_pathogenic | 0.9889 | pathogenic | -2.822 | Highly Destabilizing | 0.945 | D | 0.689 | prob.neutral | None | None | None | None | N |
| I/F | 0.5851 | likely_pathogenic | 0.5403 | ambiguous | -1.553 | Destabilizing | 0.864 | D | 0.569 | neutral | None | None | None | None | N |
| I/G | 0.9897 | likely_pathogenic | 0.9847 | pathogenic | -2.724 | Highly Destabilizing | 0.945 | D | 0.69 | prob.neutral | None | None | None | None | N |
| I/H | 0.989 | likely_pathogenic | 0.9843 | pathogenic | -2.012 | Highly Destabilizing | 0.995 | D | 0.675 | prob.neutral | None | None | None | None | N |
| I/K | 0.9757 | likely_pathogenic | 0.9678 | pathogenic | -1.744 | Destabilizing | 0.945 | D | 0.688 | prob.neutral | None | None | None | None | N |
| I/L | 0.2956 | likely_benign | 0.274 | benign | -1.213 | Destabilizing | 0.141 | N | 0.331 | neutral | None | None | None | None | N |
| I/M | 0.3003 | likely_benign | 0.2713 | benign | -1.165 | Destabilizing | 0.864 | D | 0.559 | neutral | None | None | None | None | N |
| I/N | 0.9574 | likely_pathogenic | 0.941 | pathogenic | -1.85 | Destabilizing | 0.975 | D | 0.676 | prob.neutral | None | None | None | None | N |
| I/P | 0.9882 | likely_pathogenic | 0.9844 | pathogenic | -1.559 | Destabilizing | 0.981 | D | 0.672 | neutral | None | None | None | None | N |
| I/Q | 0.9806 | likely_pathogenic | 0.9747 | pathogenic | -1.968 | Destabilizing | 0.981 | D | 0.672 | neutral | None | None | None | None | N |
| I/R | 0.9633 | likely_pathogenic | 0.9523 | pathogenic | -1.198 | Destabilizing | 0.945 | D | 0.673 | neutral | None | None | None | None | N |
| I/S | 0.9548 | likely_pathogenic | 0.9366 | pathogenic | -2.412 | Highly Destabilizing | 0.864 | D | 0.621 | neutral | None | None | None | None | N |
| I/T | 0.9098 | likely_pathogenic | 0.858 | pathogenic | -2.21 | Highly Destabilizing | 0.645 | D | 0.512 | neutral | None | None | None | None | N |
| I/V | 0.1484 | likely_benign | 0.1235 | benign | -1.559 | Destabilizing | 0.002 | N | 0.219 | neutral | None | None | None | None | N |
| I/W | 0.982 | likely_pathogenic | 0.9788 | pathogenic | -1.808 | Destabilizing | 0.995 | D | 0.685 | prob.neutral | None | None | None | None | N |
| I/Y | 0.954 | likely_pathogenic | 0.9453 | pathogenic | -1.575 | Destabilizing | 0.945 | D | 0.567 | 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.