Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 6602 | 20029;20030;20031 | chr2:178727774;178727773;178727772 | chr2:179592501;179592500;179592499 |
| N2AB | 6285 | 19078;19079;19080 | chr2:178727774;178727773;178727772 | chr2:179592501;179592500;179592499 |
| N2A | 5358 | 16297;16298;16299 | chr2:178727774;178727773;178727772 | chr2:179592501;179592500;179592499 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/Q | rs749229040  |
-0.123 | 1.0 | D | 0.635 | 0.448 | 0.492267288202 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 0 | 0 |
| P/Q | rs749229040 |
-0.123 | 1.0 | D | 0.635 | 0.448 | 0.492267288202 | gnomAD-4.0.0 | 6.3705E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 8.3227E-05 | None | 0 | 0 | 2.86113E-06 | 0 | 0 |
| P/R | rs749229040 |
None | 1.0 | N | 0.664 | 0.507 | 0.571380689955 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/R | rs749229040 |
None | 1.0 | N | 0.664 | 0.507 | 0.571380689955 | gnomAD-4.0.0 | 1.31506E-05 | None | None | None | None | I | None | 4.82719E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | None | None | 1.0 | N | 0.671 | 0.475 | 0.527908583987 | gnomAD-4.0.0 | 1.5926E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8611E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.1575 | likely_benign | 0.2149 | benign | -0.699 | Destabilizing | 0.999 | D | 0.656 | neutral | N | 0.489135823 | None | None | I |
| P/C | 0.7775 | likely_pathogenic | 0.8411 | pathogenic | -0.568 | Destabilizing | 1.0 | D | 0.666 | neutral | None | None | None | None | I |
| P/D | 0.6354 | likely_pathogenic | 0.7413 | pathogenic | -0.565 | Destabilizing | 0.999 | D | 0.649 | neutral | None | None | None | None | I |
| P/E | 0.48 | ambiguous | 0.6089 | pathogenic | -0.646 | Destabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | I |
| P/F | 0.7595 | likely_pathogenic | 0.8487 | pathogenic | -0.767 | Destabilizing | 1.0 | D | 0.623 | neutral | None | None | None | None | I |
| P/G | 0.5324 | ambiguous | 0.6749 | pathogenic | -0.878 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | I |
| P/H | 0.3961 | ambiguous | 0.5246 | ambiguous | -0.413 | Destabilizing | 1.0 | D | 0.633 | neutral | None | None | None | None | I |
| P/I | 0.5331 | ambiguous | 0.639 | pathogenic | -0.353 | Destabilizing | 1.0 | D | 0.66 | neutral | None | None | None | None | I |
| P/K | 0.5713 | likely_pathogenic | 0.7013 | pathogenic | -0.627 | Destabilizing | 1.0 | D | 0.649 | neutral | None | None | None | None | I |
| P/L | 0.2665 | likely_benign | 0.3545 | ambiguous | -0.353 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | N | 0.499201909 | None | None | I |
| P/M | 0.5902 | likely_pathogenic | 0.693 | pathogenic | -0.439 | Destabilizing | 1.0 | D | 0.637 | neutral | None | None | None | None | I |
| P/N | 0.543 | ambiguous | 0.6467 | pathogenic | -0.312 | Destabilizing | 1.0 | D | 0.673 | neutral | None | None | None | None | I |
| P/Q | 0.3278 | likely_benign | 0.458 | ambiguous | -0.532 | Destabilizing | 1.0 | D | 0.635 | neutral | D | 0.527688223 | None | None | I |
| P/R | 0.3608 | ambiguous | 0.4924 | ambiguous | -0.109 | Destabilizing | 1.0 | D | 0.664 | neutral | N | 0.494428969 | None | None | I |
| P/S | 0.2395 | likely_benign | 0.3349 | benign | -0.668 | Destabilizing | 1.0 | D | 0.671 | neutral | N | 0.503543549 | None | None | I |
| P/T | 0.2138 | likely_benign | 0.2987 | benign | -0.647 | Destabilizing | 1.0 | D | 0.665 | neutral | N | 0.487717018 | None | None | I |
| P/V | 0.3727 | ambiguous | 0.4725 | ambiguous | -0.434 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | I |
| P/W | 0.8883 | likely_pathogenic | 0.9351 | pathogenic | -0.866 | Destabilizing | 1.0 | D | 0.676 | prob.neutral | None | None | None | None | I |
| P/Y | 0.7088 | likely_pathogenic | 0.8028 | pathogenic | -0.58 | Destabilizing | 1.0 | D | 0.635 | neutral | 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.