Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 6402 | 19429;19430;19431 | chr2:178728722;178728721;178728720 | chr2:179593449;179593448;179593447 |
| N2AB | 6085 | 18478;18479;18480 | chr2:178728722;178728721;178728720 | chr2:179593449;179593448;179593447 |
| N2A | 5158 | 15697;15698;15699 | chr2:178728722;178728721;178728720 | chr2:179593449;179593448;179593447 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/T | rs1268309891  |
None | 0.001 | N | 0.359 | 0.154 | 0.31291088546 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| M/T | rs1268309891 |
None | 0.001 | N | 0.359 | 0.154 | 0.31291088546 | gnomAD-4.0.0 | 6.57117E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47037E-05 | 0 | 0 |
| M/V | rs72648954 |
-0.482 | None | N | 0.125 | 0.101 | None | gnomAD-2.1.1 | 5.29019E-03 | None | None | None | None | N | None | 5.12036E-02 | 2.95052E-03 | None | 4.8459E-03 | 0 | None | 1.31027E-04 | None | 0 | 4.61818E-04 | 3.38505E-03 |
| M/V | rs72648954 |
-0.482 | None | N | 0.125 | 0.101 | None | gnomAD-3.1.2 | 1.52917E-02 | None | None | None | None | N | None | 5.17441E-02 | 6.61688E-03 | 0 | 6.33641E-03 | 0 | None | 0 | 9.49367E-03 | 3.38126E-04 | 2.06954E-04 | 1.52964E-02 |
| M/V | rs72648954 |
-0.482 | None | N | 0.125 | 0.101 | None | 1000 genomes | 1.4976E-02 | None | None | None | None | N | None | 5.14E-02 | 8.6E-03 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| M/V | rs72648954 |
-0.482 | None | N | 0.125 | 0.101 | None | gnomAD-4.0.0 | 3.12341E-03 | None | None | None | None | N | None | 5.11521E-02 | 4.35406E-03 | None | 5.9858E-03 | 0 | None | 0 | 3.47567E-03 | 3.53203E-04 | 1.31865E-04 | 4.97018E-03 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.2106 | likely_benign | 0.188 | benign | -2.398 | Highly Destabilizing | None | N | 0.235 | neutral | None | None | None | None | N |
| M/C | 0.6399 | likely_pathogenic | 0.6584 | pathogenic | -2.103 | Highly Destabilizing | 0.132 | N | 0.637 | neutral | None | None | None | None | N |
| M/D | 0.9315 | likely_pathogenic | 0.9279 | pathogenic | -1.73 | Destabilizing | 0.018 | N | 0.436 | neutral | None | None | None | None | N |
| M/E | 0.7063 | likely_pathogenic | 0.7117 | pathogenic | -1.546 | Destabilizing | 0.008 | N | 0.359 | neutral | None | None | None | None | N |
| M/F | 0.3088 | likely_benign | 0.3216 | benign | -0.871 | Destabilizing | None | N | 0.134 | neutral | None | None | None | None | N |
| M/G | 0.5194 | ambiguous | 0.5299 | ambiguous | -2.855 | Highly Destabilizing | 0.004 | N | 0.369 | neutral | None | None | None | None | N |
| M/H | 0.7967 | likely_pathogenic | 0.799 | pathogenic | -2.162 | Highly Destabilizing | 0.316 | N | 0.63 | neutral | None | None | None | None | N |
| M/I | 0.1469 | likely_benign | 0.1446 | benign | -1.107 | Destabilizing | None | N | 0.264 | neutral | N | 0.377398187 | None | None | N |
| M/K | 0.5912 | likely_pathogenic | 0.6118 | pathogenic | -1.485 | Destabilizing | 0.006 | N | 0.368 | neutral | N | 0.46242237 | None | None | N |
| M/L | 0.141 | likely_benign | 0.1478 | benign | -1.107 | Destabilizing | None | N | 0.167 | neutral | N | 0.374568525 | None | None | N |
| M/N | 0.7447 | likely_pathogenic | 0.7039 | pathogenic | -1.687 | Destabilizing | 0.051 | N | 0.526 | neutral | None | None | None | None | N |
| M/P | 0.9625 | likely_pathogenic | 0.9732 | pathogenic | -1.517 | Destabilizing | 0.018 | N | 0.469 | neutral | None | None | None | None | N |
| M/Q | 0.4723 | ambiguous | 0.4948 | ambiguous | -1.497 | Destabilizing | 0.051 | N | 0.519 | neutral | None | None | None | None | N |
| M/R | 0.4952 | ambiguous | 0.5449 | ambiguous | -1.291 | Destabilizing | 0.013 | N | 0.503 | neutral | N | 0.492051844 | None | None | N |
| M/S | 0.4598 | ambiguous | 0.4134 | ambiguous | -2.323 | Highly Destabilizing | 0.001 | N | 0.365 | neutral | None | None | None | None | N |
| M/T | 0.2195 | likely_benign | 0.1687 | benign | -2.015 | Highly Destabilizing | 0.001 | N | 0.359 | neutral | N | 0.422575903 | None | None | N |
| M/V | 0.0467 | likely_benign | 0.0469 | benign | -1.517 | Destabilizing | None | N | 0.125 | neutral | N | 0.295547594 | None | None | N |
| M/W | 0.8598 | likely_pathogenic | 0.8951 | pathogenic | -1.054 | Destabilizing | 0.316 | N | 0.591 | neutral | None | None | None | None | N |
| M/Y | 0.7438 | likely_pathogenic | 0.7691 | pathogenic | -1.098 | Destabilizing | 0.004 | N | 0.381 | 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.