Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1535 | 4828;4829;4830 | chr2:178777462;178777461;178777460 | chr2:179642189;179642188;179642187 |
| N2AB | 1535 | 4828;4829;4830 | chr2:178777462;178777461;178777460 | chr2:179642189;179642188;179642187 |
| N2A | 1535 | 4828;4829;4830 | chr2:178777462;178777461;178777460 | chr2:179642189;179642188;179642187 |
| N2B | 1489 | 4690;4691;4692 | chr2:178777462;178777461;178777460 | chr2:179642189;179642188;179642187 |
| Novex-1 | 1489 | 4690;4691;4692 | chr2:178777462;178777461;178777460 | chr2:179642189;179642188;179642187 |
| Novex-2 | 1489 | 4690;4691;4692 | chr2:178777462;178777461;178777460 | chr2:179642189;179642188;179642187 |
| Novex-3 | 1535 | 4828;4829;4830 | chr2:178777462;178777461;178777460 | chr2:179642189;179642188;179642187 |
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 | rs2092354314  |
None | 1.0 | N | 0.604 | 0.491 | 0.545173277474 | gnomAD-4.0.0 | 3.42088E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59744E-06 | 0 | 1.65607E-05 |
| R/K | None | None | 0.997 | N | 0.507 | 0.333 | 0.465806656444 | gnomAD-4.0.0 | 1.59112E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85716E-06 | 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 | 0.8108 | likely_pathogenic | 0.871 | pathogenic | 0.071 | Stabilizing | 0.999 | D | 0.569 | neutral | None | None | None | None | I |
| R/C | 0.714 | likely_pathogenic | 0.7848 | pathogenic | -0.143 | Destabilizing | 1.0 | D | 0.78 | deleterious | None | None | None | None | I |
| R/D | 0.9265 | likely_pathogenic | 0.9529 | pathogenic | -0.272 | Destabilizing | 1.0 | D | 0.698 | prob.neutral | None | None | None | None | I |
| R/E | 0.7275 | likely_pathogenic | 0.8074 | pathogenic | -0.232 | Destabilizing | 0.999 | D | 0.635 | neutral | None | None | None | None | I |
| R/F | 0.9322 | likely_pathogenic | 0.9574 | pathogenic | -0.244 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | I |
| R/G | 0.7246 | likely_pathogenic | 0.8133 | pathogenic | -0.071 | Destabilizing | 1.0 | D | 0.604 | neutral | N | 0.509293798 | None | None | I |
| R/H | 0.3257 | likely_benign | 0.4142 | ambiguous | -0.601 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | I |
| R/I | 0.7516 | likely_pathogenic | 0.8242 | pathogenic | 0.398 | Stabilizing | 1.0 | D | 0.74 | deleterious | None | None | None | None | I |
| R/K | 0.2446 | likely_benign | 0.3036 | benign | -0.082 | Destabilizing | 0.997 | D | 0.507 | neutral | N | 0.496219056 | None | None | I |
| R/L | 0.6656 | likely_pathogenic | 0.7526 | pathogenic | 0.398 | Stabilizing | 1.0 | D | 0.604 | neutral | None | None | None | None | I |
| R/M | 0.7841 | likely_pathogenic | 0.8571 | pathogenic | -0.021 | Destabilizing | 1.0 | D | 0.704 | prob.neutral | N | 0.504729975 | None | None | I |
| R/N | 0.9085 | likely_pathogenic | 0.9417 | pathogenic | 0.059 | Stabilizing | 1.0 | D | 0.706 | prob.neutral | None | None | None | None | I |
| R/P | 0.841 | likely_pathogenic | 0.8779 | pathogenic | 0.307 | Stabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | I |
| R/Q | 0.2415 | likely_benign | 0.31 | benign | 0.005 | Stabilizing | 1.0 | D | 0.694 | prob.neutral | None | None | None | None | I |
| R/S | 0.8731 | likely_pathogenic | 0.9212 | pathogenic | -0.126 | Destabilizing | 1.0 | D | 0.645 | neutral | N | 0.472040195 | None | None | I |
| R/T | 0.7616 | likely_pathogenic | 0.8441 | pathogenic | 0.019 | Stabilizing | 1.0 | D | 0.644 | neutral | N | 0.503917449 | None | None | I |
| R/V | 0.7995 | likely_pathogenic | 0.8582 | pathogenic | 0.307 | Stabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | I |
| R/W | 0.6389 | likely_pathogenic | 0.7346 | pathogenic | -0.424 | Destabilizing | 1.0 | D | 0.799 | deleterious | D | 0.652384816 | None | None | I |
| R/Y | 0.8534 | likely_pathogenic | 0.9041 | pathogenic | -0.015 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | 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.