Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35712 | 107359;107360;107361 | chr2:178528617;178528616;178528615 | chr2:179393344;179393343;179393342 |
| N2AB | 34071 | 102436;102437;102438 | chr2:178528617;178528616;178528615 | chr2:179393344;179393343;179393342 |
| N2A | 33144 | 99655;99656;99657 | chr2:178528617;178528616;178528615 | chr2:179393344;179393343;179393342 |
| N2B | 26647 | 80164;80165;80166 | chr2:178528617;178528616;178528615 | chr2:179393344;179393343;179393342 |
| Novex-1 | 26772 | 80539;80540;80541 | chr2:178528617;178528616;178528615 | chr2:179393344;179393343;179393342 |
| Novex-2 | 26839 | 80740;80741;80742 | chr2:178528617;178528616;178528615 | chr2:179393344;179393343;179393342 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/H | rs727504949  |
-0.97 | 1.0 | N | 0.667 | 0.353 | 0.310147130316 | gnomAD-2.1.1 | 8.65E-05 | None | None | None | None | N | None | 0 | 2.86E-05 | None | 0 | 1.19443E-03 | None | 0 | None | 0 | 0 | 0 |
| N/H | rs727504949 |
-0.97 | 1.0 | N | 0.667 | 0.353 | 0.310147130316 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 5.76923E-04 | None | 0 | 0 | 0 | 0 | 0 |
| N/H | rs727504949 |
-0.97 | 1.0 | N | 0.667 | 0.353 | 0.310147130316 | gnomAD-4.0.0 | 1.61224E-05 | None | None | None | None | N | None | 0 | 1.67179E-05 | None | 0 | 5.34974E-04 | None | 0 | 0 | 0 | 0 | 1.60215E-05 |
| N/S | None | None | 0.999 | N | 0.526 | 0.335 | 0.233150807113 | gnomAD-4.0.0 | 6.84747E-07 | None | None | None | None | N | None | 2.98811E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.4817 | ambiguous | 0.5149 | ambiguous | -0.392 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| N/C | 0.5906 | likely_pathogenic | 0.6517 | pathogenic | 0.254 | Stabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| N/D | 0.2981 | likely_benign | 0.3208 | benign | 0.206 | Stabilizing | 0.999 | D | 0.569 | neutral | N | 0.46829599 | None | None | N |
| N/E | 0.6235 | likely_pathogenic | 0.6536 | pathogenic | 0.214 | Stabilizing | 0.999 | D | 0.672 | neutral | None | None | None | None | N |
| N/F | 0.7415 | likely_pathogenic | 0.771 | pathogenic | -0.561 | Destabilizing | 1.0 | D | 0.712 | prob.delet. | None | None | None | None | N |
| N/G | 0.614 | likely_pathogenic | 0.6688 | pathogenic | -0.622 | Destabilizing | 0.999 | D | 0.519 | neutral | None | None | None | None | N |
| N/H | 0.193 | likely_benign | 0.2049 | benign | -0.527 | Destabilizing | 1.0 | D | 0.667 | neutral | N | 0.48380416 | None | None | N |
| N/I | 0.2989 | likely_benign | 0.321 | benign | 0.14 | Stabilizing | 1.0 | D | 0.735 | prob.delet. | N | 0.455617481 | None | None | N |
| N/K | 0.5262 | ambiguous | 0.5377 | ambiguous | 0.029 | Stabilizing | 1.0 | D | 0.691 | prob.neutral | N | 0.449670156 | None | None | N |
| N/L | 0.3975 | ambiguous | 0.4257 | ambiguous | 0.14 | Stabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| N/M | 0.4659 | ambiguous | 0.4989 | ambiguous | 0.335 | Stabilizing | 1.0 | D | 0.642 | neutral | None | None | None | None | N |
| N/P | 0.8298 | likely_pathogenic | 0.8595 | pathogenic | -0.008 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | N |
| N/Q | 0.5546 | ambiguous | 0.5883 | pathogenic | -0.391 | Destabilizing | 1.0 | D | 0.69 | prob.neutral | None | None | None | None | N |
| N/R | 0.5932 | likely_pathogenic | 0.6085 | pathogenic | 0.032 | Stabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
| N/S | 0.1571 | likely_benign | 0.1749 | benign | -0.296 | Destabilizing | 0.999 | D | 0.526 | neutral | N | 0.417675168 | None | None | N |
| N/T | 0.2163 | likely_benign | 0.2277 | benign | -0.123 | Destabilizing | 0.999 | D | 0.669 | neutral | N | 0.360416376 | None | None | N |
| N/V | 0.3575 | ambiguous | 0.3882 | ambiguous | -0.008 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| N/W | 0.9136 | likely_pathogenic | 0.9276 | pathogenic | -0.496 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | N |
| N/Y | 0.2652 | likely_benign | 0.278 | benign | -0.244 | Destabilizing | 1.0 | D | 0.692 | prob.neutral | N | 0.473741882 | 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.