Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22881 | 68866;68867;68868 | chr2:178577785;178577784;178577783 | chr2:179442512;179442511;179442510 |
| N2AB | 21240 | 63943;63944;63945 | chr2:178577785;178577784;178577783 | chr2:179442512;179442511;179442510 |
| N2A | 20313 | 61162;61163;61164 | chr2:178577785;178577784;178577783 | chr2:179442512;179442511;179442510 |
| N2B | 13816 | 41671;41672;41673 | chr2:178577785;178577784;178577783 | chr2:179442512;179442511;179442510 |
| Novex-1 | 13941 | 42046;42047;42048 | chr2:178577785;178577784;178577783 | chr2:179442512;179442511;179442510 |
| Novex-2 | 14008 | 42247;42248;42249 | chr2:178577785;178577784;178577783 | chr2:179442512;179442511;179442510 |
| 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 | None | None | 0.71 | N | 0.532 | 0.381 | 0.470484629704 | gnomAD-4.0.0 | 9.58267E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.25953E-05 | 0 | 0 |
| R/Q | rs772700244  |
-1.407 | 0.068 | N | 0.274 | 0.211 | 0.163833314356 | gnomAD-2.1.1 | 3.63E-05 | None | None | None | None | N | None | 0 | 1.16131E-04 | None | 0 | 5.6E-05 | None | 3.27E-05 | None | 0 | 2.68E-05 | 0 |
| R/Q | rs772700244 |
-1.407 | 0.068 | N | 0.274 | 0.211 | 0.163833314356 | gnomAD-4.0.0 | 1.71113E-05 | None | None | None | None | N | None | 0 | 8.94734E-05 | None | 0 | 2.52512E-05 | None | 1.87631E-05 | 3.47464E-04 | 1.34947E-05 | 1.15993E-05 | 1.65717E-05 |
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 | 0.8016 | likely_pathogenic | 0.8046 | pathogenic | -2.17 | Highly Destabilizing | 0.345 | N | 0.477 | neutral | None | None | None | None | N |
| R/C | 0.2443 | likely_benign | 0.2503 | benign | -2.19 | Highly Destabilizing | 0.991 | D | 0.571 | neutral | None | None | None | None | N |
| R/D | 0.9745 | likely_pathogenic | 0.9724 | pathogenic | -0.943 | Destabilizing | 0.561 | D | 0.609 | neutral | None | None | None | None | N |
| R/E | 0.8006 | likely_pathogenic | 0.7907 | pathogenic | -0.771 | Destabilizing | 0.39 | N | 0.481 | neutral | None | None | None | None | N |
| R/F | 0.8841 | likely_pathogenic | 0.8851 | pathogenic | -1.767 | Destabilizing | 0.818 | D | 0.613 | neutral | None | None | None | None | N |
| R/G | 0.7342 | likely_pathogenic | 0.7272 | pathogenic | -2.477 | Highly Destabilizing | 0.71 | D | 0.532 | neutral | N | 0.494325339 | None | None | N |
| R/H | 0.2729 | likely_benign | 0.2562 | benign | -2.347 | Highly Destabilizing | 0.901 | D | 0.552 | neutral | None | None | None | None | N |
| R/I | 0.6744 | likely_pathogenic | 0.6767 | pathogenic | -1.293 | Destabilizing | 0.39 | N | 0.522 | neutral | None | None | None | None | N |
| R/K | 0.1356 | likely_benign | 0.1357 | benign | -1.779 | Destabilizing | 0.209 | N | 0.447 | neutral | None | None | None | None | N |
| R/L | 0.5037 | ambiguous | 0.4992 | ambiguous | -1.293 | Destabilizing | 0.003 | N | 0.306 | neutral | N | 0.472662685 | None | None | N |
| R/M | 0.5069 | ambiguous | 0.5348 | ambiguous | -1.593 | Destabilizing | 0.103 | N | 0.279 | neutral | None | None | None | None | N |
| R/N | 0.9121 | likely_pathogenic | 0.9063 | pathogenic | -1.417 | Destabilizing | 0.561 | D | 0.536 | neutral | None | None | None | None | N |
| R/P | 0.9931 | likely_pathogenic | 0.9932 | pathogenic | -1.573 | Destabilizing | 0.946 | D | 0.619 | neutral | D | 0.533914437 | None | None | N |
| R/Q | 0.1753 | likely_benign | 0.1763 | benign | -1.519 | Destabilizing | 0.068 | N | 0.274 | neutral | N | 0.516806721 | None | None | N |
| R/S | 0.9131 | likely_pathogenic | 0.9086 | pathogenic | -2.439 | Highly Destabilizing | 0.561 | D | 0.542 | neutral | None | None | None | None | N |
| R/T | 0.7525 | likely_pathogenic | 0.7702 | pathogenic | -2.071 | Highly Destabilizing | 0.561 | D | 0.544 | neutral | None | None | None | None | N |
| R/V | 0.7385 | likely_pathogenic | 0.7429 | pathogenic | -1.573 | Destabilizing | 0.209 | N | 0.459 | neutral | None | None | None | None | N |
| R/W | 0.525 | ambiguous | 0.5167 | ambiguous | -1.215 | Destabilizing | 0.991 | D | 0.58 | neutral | None | None | None | None | N |
| R/Y | 0.7344 | likely_pathogenic | 0.7273 | pathogenic | -1.044 | Destabilizing | 0.965 | D | 0.601 | 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.