Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33333 | 100222;100223;100224 | chr2:178537112;178537111;178537110 | chr2:179401839;179401838;179401837 |
| N2AB | 31692 | 95299;95300;95301 | chr2:178537112;178537111;178537110 | chr2:179401839;179401838;179401837 |
| N2A | 30765 | 92518;92519;92520 | chr2:178537112;178537111;178537110 | chr2:179401839;179401838;179401837 |
| N2B | 24268 | 73027;73028;73029 | chr2:178537112;178537111;178537110 | chr2:179401839;179401838;179401837 |
| Novex-1 | 24393 | 73402;73403;73404 | chr2:178537112;178537111;178537110 | chr2:179401839;179401838;179401837 |
| Novex-2 | 24460 | 73603;73604;73605 | chr2:178537112;178537111;178537110 | chr2:179401839;179401838;179401837 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/G | rs746653975  |
-1.165 | 1.0 | N | 0.607 | 0.363 | 0.287603790349 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 2.91E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| A/G | rs746653975 |
-1.165 | 1.0 | N | 0.607 | 0.363 | 0.287603790349 | gnomAD-4.0.0 | 6.84463E-07 | None | None | None | None | N | None | 0 | 2.24034E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/P | rs1171018948 |
-0.275 | 1.0 | N | 0.733 | 0.501 | 0.341226946553 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.6E-05 | None | 0 | None | 0 | 0 | 0 |
| A/V | None | None | 1.0 | N | 0.671 | 0.379 | 0.297375071883 | gnomAD-4.0.0 | 6.84463E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99625E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.724 | likely_pathogenic | 0.7377 | pathogenic | -0.549 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| A/D | 0.4623 | ambiguous | 0.4572 | ambiguous | -0.968 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | N | 0.459355927 | None | None | N |
| A/E | 0.4247 | ambiguous | 0.4514 | ambiguous | -0.983 | Destabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | N |
| A/F | 0.6071 | likely_pathogenic | 0.6136 | pathogenic | -0.917 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| A/G | 0.2217 | likely_benign | 0.2252 | benign | -1.107 | Destabilizing | 1.0 | D | 0.607 | neutral | N | 0.457702489 | None | None | N |
| A/H | 0.7664 | likely_pathogenic | 0.7738 | pathogenic | -1.178 | Destabilizing | 1.0 | D | 0.674 | neutral | None | None | None | None | N |
| A/I | 0.458 | ambiguous | 0.4729 | ambiguous | -0.3 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | N |
| A/K | 0.7153 | likely_pathogenic | 0.7313 | pathogenic | -1.061 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| A/L | 0.3356 | likely_benign | 0.3525 | ambiguous | -0.3 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | N |
| A/M | 0.446 | ambiguous | 0.4569 | ambiguous | -0.206 | Destabilizing | 1.0 | D | 0.663 | neutral | None | None | None | None | N |
| A/N | 0.4544 | ambiguous | 0.4459 | ambiguous | -0.742 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| A/P | 0.5664 | likely_pathogenic | 0.588 | pathogenic | -0.444 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | N | 0.46695669 | None | None | N |
| A/Q | 0.544 | ambiguous | 0.5648 | pathogenic | -0.876 | Destabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | N |
| A/R | 0.6454 | likely_pathogenic | 0.676 | pathogenic | -0.707 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | N |
| A/S | 0.1398 | likely_benign | 0.139 | benign | -1.085 | Destabilizing | 1.0 | D | 0.613 | neutral | N | 0.439250014 | None | None | N |
| A/T | 0.1991 | likely_benign | 0.2028 | benign | -1.007 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | N | 0.400923699 | None | None | N |
| A/V | 0.2254 | likely_benign | 0.2312 | benign | -0.444 | Destabilizing | 1.0 | D | 0.671 | neutral | N | 0.414583643 | None | None | N |
| A/W | 0.872 | likely_pathogenic | 0.891 | pathogenic | -1.279 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| A/Y | 0.6828 | likely_pathogenic | 0.6801 | pathogenic | -0.86 | Destabilizing | 1.0 | D | 0.698 | prob.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.