Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18065 | 54418;54419;54420 | chr2:178604896;178604895;178604894 | chr2:179469623;179469622;179469621 |
| N2AB | 16424 | 49495;49496;49497 | chr2:178604896;178604895;178604894 | chr2:179469623;179469622;179469621 |
| N2A | 15497 | 46714;46715;46716 | chr2:178604896;178604895;178604894 | chr2:179469623;179469622;179469621 |
| N2B | 9000 | 27223;27224;27225 | chr2:178604896;178604895;178604894 | chr2:179469623;179469622;179469621 |
| Novex-1 | 9125 | 27598;27599;27600 | chr2:178604896;178604895;178604894 | chr2:179469623;179469622;179469621 |
| Novex-2 | 9192 | 27799;27800;27801 | chr2:178604896;178604895;178604894 | chr2:179469623;179469622;179469621 |
| 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 | rs369438623  |
-0.759 | 1.0 | N | 0.873 | 0.418 | None | gnomAD-2.1.1 | 1.22E-05 | None | None | None | None | I | None | 6.49E-05 | 2.94E-05 | None | 0 | 5.66E-05 | None | 0 | None | 0 | 0 | 0 |
| R/C | rs369438623 |
-0.759 | 1.0 | N | 0.873 | 0.418 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 2.42E-05 | 6.57E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/C | rs369438623 |
-0.759 | 1.0 | N | 0.873 | 0.418 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/C | rs369438623 |
-0.759 | 1.0 | N | 0.873 | 0.418 | None | gnomAD-4.0.0 | 7.45221E-06 | None | None | None | None | I | None | 4.01273E-05 | 5.03423E-05 | None | 0 | 0 | None | 0 | 0 | 1.69765E-06 | 3.3125E-05 | 1.60462E-05 |
| R/H | rs375895183 |
-1.416 | 1.0 | N | 0.753 | 0.353 | None | gnomAD-2.1.1 | 6.5E-05 | None | None | None | None | I | None | 0 | 5.86E-05 | None | 0 | 2.82358E-04 | None | 0 | None | 4.68E-05 | 7.18E-05 | 0 |
| R/H | rs375895183 |
-1.416 | 1.0 | N | 0.753 | 0.353 | None | gnomAD-3.1.2 | 4.61E-05 | None | None | None | None | I | None | 2.42E-05 | 6.57E-05 | 0 | 0 | 3.90625E-04 | None | 0 | 0 | 4.42E-05 | 0 | 0 |
| R/H | rs375895183 |
-1.416 | 1.0 | N | 0.753 | 0.353 | None | gnomAD-4.0.0 | 9.19224E-05 | None | None | None | None | I | None | 1.33933E-05 | 6.70848E-05 | None | 3.39466E-05 | 2.01712E-04 | None | 0 | 0 | 1.09502E-04 | 2.21078E-05 | 3.21007E-05 |
| R/P | rs375895183 |
None | 1.0 | N | 0.826 | 0.439 | 0.350088858571 | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/P | rs375895183 |
None | 1.0 | N | 0.826 | 0.439 | 0.350088858571 | gnomAD-4.0.0 | 6.59092E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47306E-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 | 0.763 | likely_pathogenic | 0.6725 | pathogenic | -0.312 | Destabilizing | 0.998 | D | 0.571 | neutral | None | None | None | None | I |
| R/C | 0.333 | likely_benign | 0.2563 | benign | -0.279 | Destabilizing | 1.0 | D | 0.873 | deleterious | N | 0.469049882 | None | None | I |
| R/D | 0.9742 | likely_pathogenic | 0.9582 | pathogenic | -0.06 | Destabilizing | 0.999 | D | 0.839 | deleterious | None | None | None | None | I |
| R/E | 0.7897 | likely_pathogenic | 0.706 | pathogenic | 0.002 | Stabilizing | 0.998 | D | 0.651 | prob.neutral | None | None | None | None | I |
| R/F | 0.8897 | likely_pathogenic | 0.8309 | pathogenic | -0.494 | Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | I |
| R/G | 0.8127 | likely_pathogenic | 0.7173 | pathogenic | -0.526 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | N | 0.486482574 | None | None | I |
| R/H | 0.3105 | likely_benign | 0.2509 | benign | -0.918 | Destabilizing | 1.0 | D | 0.753 | deleterious | N | 0.468796393 | None | None | I |
| R/I | 0.4742 | ambiguous | 0.376 | ambiguous | 0.225 | Stabilizing | 0.999 | D | 0.856 | deleterious | None | None | None | None | I |
| R/K | 0.1476 | likely_benign | 0.1438 | benign | -0.306 | Destabilizing | 0.995 | D | 0.525 | neutral | None | None | None | None | I |
| R/L | 0.6062 | likely_pathogenic | 0.5018 | ambiguous | 0.225 | Stabilizing | 1.0 | D | 0.713 | prob.delet. | N | 0.510925606 | None | None | I |
| R/M | 0.649 | likely_pathogenic | 0.5556 | ambiguous | -0.018 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | I |
| R/N | 0.9144 | likely_pathogenic | 0.8736 | pathogenic | 0.148 | Stabilizing | 0.999 | D | 0.745 | deleterious | None | None | None | None | I |
| R/P | 0.85 | likely_pathogenic | 0.809 | pathogenic | 0.066 | Stabilizing | 1.0 | D | 0.826 | deleterious | N | 0.479215833 | None | None | I |
| R/Q | 0.233 | likely_benign | 0.1885 | benign | -0.076 | Destabilizing | 0.999 | D | 0.759 | deleterious | None | None | None | None | I |
| R/S | 0.8735 | likely_pathogenic | 0.809 | pathogenic | -0.394 | Destabilizing | 1.0 | D | 0.763 | deleterious | N | 0.509522884 | None | None | I |
| R/T | 0.61 | likely_pathogenic | 0.4977 | ambiguous | -0.193 | Destabilizing | 0.999 | D | 0.761 | deleterious | None | None | None | None | I |
| R/V | 0.5331 | ambiguous | 0.4449 | ambiguous | 0.066 | Stabilizing | 0.999 | D | 0.801 | deleterious | None | None | None | None | I |
| R/W | 0.6567 | likely_pathogenic | 0.5584 | ambiguous | -0.394 | Destabilizing | 1.0 | D | 0.886 | deleterious | None | None | None | None | I |
| R/Y | 0.7985 | likely_pathogenic | 0.7263 | pathogenic | -0.021 | Destabilizing | 0.999 | D | 0.886 | 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.