Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18939 | 57040;57041;57042 | chr2:178598895;178598894;178598893 | chr2:179463622;179463621;179463620 |
| N2AB | 17298 | 52117;52118;52119 | chr2:178598895;178598894;178598893 | chr2:179463622;179463621;179463620 |
| N2A | 16371 | 49336;49337;49338 | chr2:178598895;178598894;178598893 | chr2:179463622;179463621;179463620 |
| N2B | 9874 | 29845;29846;29847 | chr2:178598895;178598894;178598893 | chr2:179463622;179463621;179463620 |
| Novex-1 | 9999 | 30220;30221;30222 | chr2:178598895;178598894;178598893 | chr2:179463622;179463621;179463620 |
| Novex-2 | 10066 | 30421;30422;30423 | chr2:178598895;178598894;178598893 | chr2:179463622;179463621;179463620 |
| 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/M | rs757376568  |
-0.527 | 1.0 | N | 0.725 | 0.398 | 0.370424759081 | gnomAD-4.0.0 | 4.77715E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.76563E-05 | 0 | 0 | 0 | 3.02554E-05 |
| I/N | None | None | 1.0 | N | 0.783 | 0.509 | 0.839279901858 | gnomAD-4.0.0 | 6.00161E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.56251E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9243 | likely_pathogenic | 0.9377 | pathogenic | -2.285 | Highly Destabilizing | 0.999 | D | 0.457 | neutral | None | None | None | None | N |
| I/C | 0.9329 | likely_pathogenic | 0.9556 | pathogenic | -1.3 | Destabilizing | 1.0 | D | 0.748 | deleterious | None | None | None | None | N |
| I/D | 0.9966 | likely_pathogenic | 0.9965 | pathogenic | -2.969 | Highly Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | N |
| I/E | 0.9808 | likely_pathogenic | 0.9798 | pathogenic | -2.677 | Highly Destabilizing | 1.0 | D | 0.758 | deleterious | None | None | None | None | N |
| I/F | 0.7407 | likely_pathogenic | 0.7361 | pathogenic | -1.436 | Destabilizing | 1.0 | D | 0.702 | prob.neutral | N | 0.473735415 | None | None | N |
| I/G | 0.9886 | likely_pathogenic | 0.9904 | pathogenic | -2.846 | Highly Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| I/H | 0.9885 | likely_pathogenic | 0.9885 | pathogenic | -2.5 | Highly Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| I/K | 0.9728 | likely_pathogenic | 0.97 | pathogenic | -1.679 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | N |
| I/L | 0.2166 | likely_benign | 0.2426 | benign | -0.62 | Destabilizing | 0.993 | D | 0.381 | neutral | N | 0.502106627 | None | None | N |
| I/M | 0.3344 | likely_benign | 0.3617 | ambiguous | -0.562 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | N | 0.485256304 | None | None | N |
| I/N | 0.9685 | likely_pathogenic | 0.9687 | pathogenic | -2.282 | Highly Destabilizing | 1.0 | D | 0.783 | deleterious | N | 0.469933072 | None | None | N |
| I/P | 0.9854 | likely_pathogenic | 0.982 | pathogenic | -1.163 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | N |
| I/Q | 0.9637 | likely_pathogenic | 0.959 | pathogenic | -2.006 | Highly Destabilizing | 1.0 | D | 0.776 | deleterious | None | None | None | None | N |
| I/R | 0.9658 | likely_pathogenic | 0.9596 | pathogenic | -1.717 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| I/S | 0.9623 | likely_pathogenic | 0.9645 | pathogenic | -2.842 | Highly Destabilizing | 1.0 | D | 0.693 | prob.neutral | N | 0.515494425 | None | None | N |
| I/T | 0.9344 | likely_pathogenic | 0.9485 | pathogenic | -2.394 | Highly Destabilizing | 1.0 | D | 0.677 | prob.neutral | N | 0.488691826 | None | None | N |
| I/V | 0.0885 | likely_benign | 0.1192 | benign | -1.163 | Destabilizing | 0.993 | D | 0.352 | neutral | N | 0.412004698 | None | None | N |
| I/W | 0.9904 | likely_pathogenic | 0.9885 | pathogenic | -1.869 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| I/Y | 0.9742 | likely_pathogenic | 0.9709 | pathogenic | -1.527 | Destabilizing | 1.0 | D | 0.765 | deleterious | 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.