Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18473 | 55642;55643;55644 | chr2:178601673;178601672;178601671 | chr2:179466400;179466399;179466398 |
| N2AB | 16832 | 50719;50720;50721 | chr2:178601673;178601672;178601671 | chr2:179466400;179466399;179466398 |
| N2A | 15905 | 47938;47939;47940 | chr2:178601673;178601672;178601671 | chr2:179466400;179466399;179466398 |
| N2B | 9408 | 28447;28448;28449 | chr2:178601673;178601672;178601671 | chr2:179466400;179466399;179466398 |
| Novex-1 | 9533 | 28822;28823;28824 | chr2:178601673;178601672;178601671 | chr2:179466400;179466399;179466398 |
| Novex-2 | 9600 | 29023;29024;29025 | chr2:178601673;178601672;178601671 | chr2:179466400;179466399;179466398 |
| 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/G | rs72646822  |
-0.848 | 1.0 | N | 0.707 | 0.5 | None | gnomAD-2.1.1 | 1.65709E-04 | None | None | None | None | I | None | 1.71519E-03 | 6.22E-05 | None | 0 | 0 | None | 0 | None | 0 | 8.09E-06 | 0 |
| R/G | rs72646822 |
-0.848 | 1.0 | N | 0.707 | 0.5 | None | gnomAD-3.1.2 | 4.2087E-04 | None | None | None | None | I | None | 1.49556E-03 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.78469E-04 |
| R/G | rs72646822 |
-0.848 | 1.0 | N | 0.707 | 0.5 | None | 1000 genomes | 5.99042E-04 | None | None | None | None | I | None | 2.3E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/G | rs72646822 |
-0.848 | 1.0 | N | 0.707 | 0.5 | None | gnomAD-4.0.0 | 8.6278E-05 | None | None | None | None | I | None | 1.70298E-03 | 1.05787E-04 | None | 0 | 0 | None | 0 | 0 | 8.50589E-07 | 0 | 8.09297E-05 |
| R/S | None | None | 1.0 | N | 0.735 | 0.508 | 0.394685799254 | gnomAD-4.0.0 | 1.62881E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8928E-06 | 0 | 0 |
| R/T | rs2053488389 |
None | 1.0 | N | 0.725 | 0.499 | 0.465721554213 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/T | rs2053488389 |
None | 1.0 | N | 0.725 | 0.499 | 0.465721554213 | gnomAD-4.0.0 | 6.57825E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47128E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.5774 | likely_pathogenic | 0.5098 | ambiguous | -0.202 | Destabilizing | 0.999 | D | 0.639 | neutral | None | None | None | None | I |
| R/C | 0.2739 | likely_benign | 0.2489 | benign | -0.156 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | I |
| R/D | 0.7937 | likely_pathogenic | 0.7348 | pathogenic | 0.07 | Stabilizing | 1.0 | D | 0.74 | deleterious | None | None | None | None | I |
| R/E | 0.6022 | likely_pathogenic | 0.539 | ambiguous | 0.168 | Stabilizing | 0.999 | D | 0.632 | neutral | None | None | None | None | I |
| R/F | 0.5791 | likely_pathogenic | 0.5295 | ambiguous | -0.206 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | I |
| R/G | 0.539 | ambiguous | 0.4766 | ambiguous | -0.472 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | N | 0.485465747 | None | None | I |
| R/H | 0.1384 | likely_benign | 0.1272 | benign | -0.937 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | I |
| R/I | 0.2748 | likely_benign | 0.2478 | benign | 0.499 | Stabilizing | 1.0 | D | 0.728 | prob.delet. | N | 0.497984178 | None | None | I |
| R/K | 0.1497 | likely_benign | 0.1342 | benign | -0.196 | Destabilizing | 0.997 | D | 0.483 | neutral | N | 0.46483161 | None | None | I |
| R/L | 0.2915 | likely_benign | 0.2603 | benign | 0.499 | Stabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | I |
| R/M | 0.3188 | likely_benign | 0.2846 | benign | 0.1 | Stabilizing | 1.0 | D | 0.718 | prob.delet. | None | None | None | None | I |
| R/N | 0.6698 | likely_pathogenic | 0.606 | pathogenic | 0.229 | Stabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | I |
| R/P | 0.824 | likely_pathogenic | 0.771 | pathogenic | 0.288 | Stabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | I |
| R/Q | 0.1713 | likely_benign | 0.1539 | benign | 0.088 | Stabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | I |
| R/S | 0.6447 | likely_pathogenic | 0.5742 | pathogenic | -0.313 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | N | 0.474104454 | None | None | I |
| R/T | 0.3139 | likely_benign | 0.2725 | benign | -0.05 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | N | 0.460079151 | None | None | I |
| R/V | 0.3738 | ambiguous | 0.329 | benign | 0.288 | Stabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | I |
| R/W | 0.2248 | likely_benign | 0.2047 | benign | -0.069 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | I |
| R/Y | 0.4589 | ambiguous | 0.4184 | ambiguous | 0.296 | Stabilizing | 1.0 | D | 0.743 | deleterious | 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.