Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33221 | 99886;99887;99888 | chr2:178537546;178537545;178537544 | chr2:179402273;179402272;179402271 |
| N2AB | 31580 | 94963;94964;94965 | chr2:178537546;178537545;178537544 | chr2:179402273;179402272;179402271 |
| N2A | 30653 | 92182;92183;92184 | chr2:178537546;178537545;178537544 | chr2:179402273;179402272;179402271 |
| N2B | 24156 | 72691;72692;72693 | chr2:178537546;178537545;178537544 | chr2:179402273;179402272;179402271 |
| Novex-1 | 24281 | 73066;73067;73068 | chr2:178537546;178537545;178537544 | chr2:179402273;179402272;179402271 |
| Novex-2 | 24348 | 73267;73268;73269 | chr2:178537546;178537545;178537544 | chr2:179402273;179402272;179402271 |
| 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 | rs938263270  |
None | 0.983 | N | 0.346 | 0.331 | 0.609990207021 | gnomAD-4.0.0 | 6.84242E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99486E-07 | 0 | 0 |
| I/T | rs1306714947 |
None | 1.0 | N | 0.547 | 0.489 | 0.710785509443 | gnomAD-4.0.0 | 4.78971E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.00801E-04 | None | 0 | 0 | 1.79898E-06 | 1.15937E-05 | 0 |
| I/V | rs938263270 |
-1.589 | 0.987 | N | 0.343 | 0.256 | 0.690830541769 | gnomAD-2.1.1 | 3.18E-05 | None | None | None | None | N | None | 1.14811E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs938263270 |
-1.589 | 0.987 | N | 0.343 | 0.256 | 0.690830541769 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 9.65E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs938263270 |
-1.589 | 0.987 | N | 0.343 | 0.256 | 0.690830541769 | gnomAD-4.0.0 | 3.71827E-06 | None | None | None | None | N | None | 8.00918E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.4903 | ambiguous | 0.5059 | ambiguous | -0.622 | Destabilizing | 1.0 | D | 0.467 | neutral | None | None | None | None | N |
| I/C | 0.9064 | likely_pathogenic | 0.9089 | pathogenic | -0.903 | Destabilizing | 1.0 | D | 0.613 | neutral | None | None | None | None | N |
| I/D | 0.938 | likely_pathogenic | 0.9176 | pathogenic | -0.25 | Destabilizing | 1.0 | D | 0.644 | neutral | None | None | None | None | N |
| I/E | 0.8405 | likely_pathogenic | 0.7888 | pathogenic | -0.309 | Destabilizing | 1.0 | D | 0.648 | neutral | None | None | None | None | N |
| I/F | 0.3628 | ambiguous | 0.3834 | ambiguous | -0.612 | Destabilizing | 1.0 | D | 0.575 | neutral | N | 0.490615489 | None | None | N |
| I/G | 0.8941 | likely_pathogenic | 0.895 | pathogenic | -0.748 | Destabilizing | 1.0 | D | 0.643 | neutral | None | None | None | None | N |
| I/H | 0.8208 | likely_pathogenic | 0.781 | pathogenic | 0.104 | Stabilizing | 1.0 | D | 0.664 | neutral | None | None | None | None | N |
| I/K | 0.6581 | likely_pathogenic | 0.6063 | pathogenic | -0.414 | Destabilizing | 0.999 | D | 0.646 | neutral | None | None | None | None | N |
| I/L | 0.2282 | likely_benign | 0.2373 | benign | -0.392 | Destabilizing | 0.983 | D | 0.346 | neutral | N | 0.476531471 | None | None | N |
| I/M | 0.1823 | likely_benign | 0.1901 | benign | -0.777 | Destabilizing | 1.0 | D | 0.587 | neutral | N | 0.47185637 | None | None | N |
| I/N | 0.683 | likely_pathogenic | 0.6452 | pathogenic | -0.418 | Destabilizing | 1.0 | D | 0.666 | neutral | N | 0.482110649 | None | None | N |
| I/P | 0.9717 | likely_pathogenic | 0.9731 | pathogenic | -0.442 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | N |
| I/Q | 0.7376 | likely_pathogenic | 0.6771 | pathogenic | -0.546 | Destabilizing | 1.0 | D | 0.663 | neutral | None | None | None | None | N |
| I/R | 0.5201 | ambiguous | 0.4715 | ambiguous | 0.05 | Stabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | N |
| I/S | 0.5184 | ambiguous | 0.4862 | ambiguous | -0.82 | Destabilizing | 1.0 | D | 0.595 | neutral | N | 0.431988473 | None | None | N |
| I/T | 0.2147 | likely_benign | 0.2154 | benign | -0.775 | Destabilizing | 1.0 | D | 0.547 | neutral | N | 0.44149339 | None | None | N |
| I/V | 0.1044 | likely_benign | 0.1117 | benign | -0.442 | Destabilizing | 0.987 | D | 0.343 | neutral | N | 0.457772352 | None | None | N |
| I/W | 0.9157 | likely_pathogenic | 0.91 | pathogenic | -0.621 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| I/Y | 0.8175 | likely_pathogenic | 0.7888 | pathogenic | -0.411 | Destabilizing | 1.0 | D | 0.609 | 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.