Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29333 | 88222;88223;88224 | chr2:178557265;178557264;178557263 | chr2:179421992;179421991;179421990 |
| N2AB | 27692 | 83299;83300;83301 | chr2:178557265;178557264;178557263 | chr2:179421992;179421991;179421990 |
| N2A | 26765 | 80518;80519;80520 | chr2:178557265;178557264;178557263 | chr2:179421992;179421991;179421990 |
| N2B | 20268 | 61027;61028;61029 | chr2:178557265;178557264;178557263 | chr2:179421992;179421991;179421990 |
| Novex-1 | 20393 | 61402;61403;61404 | chr2:178557265;178557264;178557263 | chr2:179421992;179421991;179421990 |
| Novex-2 | 20460 | 61603;61604;61605 | chr2:178557265;178557264;178557263 | chr2:179421992;179421991;179421990 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/L | rs1701876010  |
None | 0.985 | N | 0.353 | 0.291 | 0.440810947182 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/L | rs1701876010 |
None | 0.985 | N | 0.353 | 0.291 | 0.440810947182 | gnomAD-4.0.0 | 6.5703E-06 | None | None | None | None | N | None | 2.41208E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs764532002 |
-0.694 | 0.999 | N | 0.649 | 0.425 | 0.519837540645 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 8.91E-06 | 0 |
| I/T | rs764532002 |
-0.694 | 0.999 | N | 0.649 | 0.425 | 0.519837540645 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07297E-04 | 0 |
| I/T | rs764532002 |
-0.694 | 0.999 | N | 0.649 | 0.425 | 0.519837540645 | gnomAD-4.0.0 | 1.23934E-05 | None | None | None | None | N | None | 0 | 1.66644E-05 | None | 0 | 0 | None | 0 | 0 | 1.18658E-05 | 4.39174E-05 | 1.60123E-05 |
| I/V | rs1701876010 |
None | 0.985 | N | 0.305 | 0.202 | 0.44153150616 | gnomAD-4.0.0 | 4.78942E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.39654E-06 | 0 | 1.65673E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.4316 | ambiguous | 0.4149 | ambiguous | -0.959 | Destabilizing | 0.998 | D | 0.534 | neutral | None | None | None | None | N |
| I/C | 0.8741 | likely_pathogenic | 0.8729 | pathogenic | -0.733 | Destabilizing | 1.0 | D | 0.633 | neutral | None | None | None | None | N |
| I/D | 0.9559 | likely_pathogenic | 0.9442 | pathogenic | -0.234 | Destabilizing | 0.999 | D | 0.747 | deleterious | None | None | None | None | N |
| I/E | 0.8629 | likely_pathogenic | 0.8297 | pathogenic | -0.303 | Destabilizing | 0.999 | D | 0.752 | deleterious | None | None | None | None | N |
| I/F | 0.4185 | ambiguous | 0.3797 | ambiguous | -0.83 | Destabilizing | 0.999 | D | 0.635 | neutral | N | 0.48883818 | None | None | N |
| I/G | 0.8684 | likely_pathogenic | 0.8585 | pathogenic | -1.171 | Destabilizing | 0.999 | D | 0.765 | deleterious | None | None | None | None | N |
| I/H | 0.8742 | likely_pathogenic | 0.8553 | pathogenic | -0.43 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| I/K | 0.7237 | likely_pathogenic | 0.6697 | pathogenic | -0.521 | Destabilizing | 0.999 | D | 0.753 | deleterious | None | None | None | None | N |
| I/L | 0.1744 | likely_benign | 0.1697 | benign | -0.508 | Destabilizing | 0.985 | D | 0.353 | neutral | N | 0.419226166 | None | None | N |
| I/M | 0.1383 | likely_benign | 0.1315 | benign | -0.445 | Destabilizing | 0.999 | D | 0.609 | neutral | N | 0.452013375 | None | None | N |
| I/N | 0.7478 | likely_pathogenic | 0.6936 | pathogenic | -0.315 | Destabilizing | 0.999 | D | 0.8 | deleterious | N | 0.508213375 | None | None | N |
| I/P | 0.9604 | likely_pathogenic | 0.9615 | pathogenic | -0.624 | Destabilizing | 0.999 | D | 0.803 | deleterious | None | None | None | None | N |
| I/Q | 0.7396 | likely_pathogenic | 0.7132 | pathogenic | -0.537 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| I/R | 0.572 | likely_pathogenic | 0.5149 | ambiguous | 0.044 | Stabilizing | 0.999 | D | 0.797 | deleterious | None | None | None | None | N |
| I/S | 0.5806 | likely_pathogenic | 0.5398 | ambiguous | -0.853 | Destabilizing | 0.999 | D | 0.737 | deleterious | N | 0.436235846 | None | None | N |
| I/T | 0.2677 | likely_benign | 0.2406 | benign | -0.809 | Destabilizing | 0.999 | D | 0.649 | prob.neutral | N | 0.421901112 | None | None | N |
| I/V | 0.093 | likely_benign | 0.0933 | benign | -0.624 | Destabilizing | 0.985 | D | 0.305 | neutral | N | 0.421170394 | None | None | N |
| I/W | 0.9076 | likely_pathogenic | 0.9018 | pathogenic | -0.833 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | N |
| I/Y | 0.848 | likely_pathogenic | 0.8257 | pathogenic | -0.59 | Destabilizing | 0.999 | D | 0.628 | 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.