Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19465 | 58618;58619;58620 | chr2:178594000;178593999;178593998 | chr2:179458727;179458726;179458725 |
| N2AB | 17824 | 53695;53696;53697 | chr2:178594000;178593999;178593998 | chr2:179458727;179458726;179458725 |
| N2A | 16897 | 50914;50915;50916 | chr2:178594000;178593999;178593998 | chr2:179458727;179458726;179458725 |
| N2B | 10400 | 31423;31424;31425 | chr2:178594000;178593999;178593998 | chr2:179458727;179458726;179458725 |
| Novex-1 | 10525 | 31798;31799;31800 | chr2:178594000;178593999;178593998 | chr2:179458727;179458726;179458725 |
| Novex-2 | 10592 | 31999;32000;32001 | chr2:178594000;178593999;178593998 | chr2:179458727;179458726;179458725 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs571477228  |
-0.093 | 0.051 | N | 0.441 | 0.221 | 0.335414705075 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| T/I | rs571477228 |
-0.093 | 0.051 | N | 0.441 | 0.221 | 0.335414705075 | gnomAD-4.0.0 | 1.59172E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85912E-06 | 0 | 0 |
| T/R | rs571477228 |
0.233 | 0.669 | N | 0.487 | 0.329 | 0.422160833541 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.59E-05 | None | 0 | None | 0 | 0 | 0 |
| T/R | rs571477228 |
0.233 | 0.669 | N | 0.487 | 0.329 | 0.422160833541 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 3.8835E-04 | None | 0 | 0 | 0 | 0 | 0 |
| T/R | rs571477228 |
0.233 | 0.669 | N | 0.487 | 0.329 | 0.422160833541 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| T/R | rs571477228 |
0.233 | 0.669 | N | 0.487 | 0.329 | 0.422160833541 | gnomAD-4.0.0 | 3.8439E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 7.29076E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0865 | likely_benign | 0.0841 | benign | -0.252 | Destabilizing | 0.022 | N | 0.231 | neutral | N | 0.413210711 | None | None | I |
| T/C | 0.3497 | ambiguous | 0.3838 | ambiguous | -0.25 | Destabilizing | 0.998 | D | 0.549 | neutral | None | None | None | None | I |
| T/D | 0.7726 | likely_pathogenic | 0.7328 | pathogenic | 0.025 | Stabilizing | 0.842 | D | 0.509 | neutral | None | None | None | None | I |
| T/E | 0.6695 | likely_pathogenic | 0.6199 | pathogenic | -0.073 | Destabilizing | 0.842 | D | 0.468 | neutral | None | None | None | None | I |
| T/F | 0.4037 | ambiguous | 0.3653 | ambiguous | -0.954 | Destabilizing | 0.974 | D | 0.626 | neutral | None | None | None | None | I |
| T/G | 0.3614 | ambiguous | 0.3482 | ambiguous | -0.289 | Destabilizing | 0.525 | D | 0.546 | neutral | None | None | None | None | I |
| T/H | 0.4629 | ambiguous | 0.4382 | ambiguous | -0.565 | Destabilizing | 0.998 | D | 0.633 | neutral | None | None | None | None | I |
| T/I | 0.3068 | likely_benign | 0.2967 | benign | -0.272 | Destabilizing | 0.051 | N | 0.441 | neutral | N | 0.459561863 | None | None | I |
| T/K | 0.58 | likely_pathogenic | 0.5342 | ambiguous | -0.219 | Destabilizing | 0.051 | N | 0.367 | neutral | N | 0.473973955 | None | None | I |
| T/L | 0.1736 | likely_benign | 0.1551 | benign | -0.272 | Destabilizing | 0.525 | D | 0.473 | neutral | None | None | None | None | I |
| T/M | 0.1292 | likely_benign | 0.1165 | benign | -0.105 | Destabilizing | 0.974 | D | 0.545 | neutral | None | None | None | None | I |
| T/N | 0.2776 | likely_benign | 0.2691 | benign | -0.005 | Destabilizing | 0.842 | D | 0.4 | neutral | None | None | None | None | I |
| T/P | 0.5874 | likely_pathogenic | 0.559 | ambiguous | -0.244 | Destabilizing | 0.966 | D | 0.511 | neutral | N | 0.491532588 | None | None | I |
| T/Q | 0.498 | ambiguous | 0.4693 | ambiguous | -0.228 | Destabilizing | 0.949 | D | 0.526 | neutral | None | None | None | None | I |
| T/R | 0.4804 | ambiguous | 0.4276 | ambiguous | 0.002 | Stabilizing | 0.669 | D | 0.487 | neutral | N | 0.511145477 | None | None | I |
| T/S | 0.1565 | likely_benign | 0.1528 | benign | -0.162 | Destabilizing | 0.051 | N | 0.233 | neutral | N | 0.459388505 | None | None | I |
| T/V | 0.192 | likely_benign | 0.1934 | benign | -0.244 | Destabilizing | 0.525 | D | 0.395 | neutral | None | None | None | None | I |
| T/W | 0.7927 | likely_pathogenic | 0.7592 | pathogenic | -1.026 | Destabilizing | 0.998 | D | 0.634 | neutral | None | None | None | None | I |
| T/Y | 0.4812 | ambiguous | 0.4532 | ambiguous | -0.711 | Destabilizing | 0.991 | D | 0.623 | 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.