Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15242 | 45949;45950;45951 | chr2:178620886;178620885;178620884 | chr2:179485613;179485612;179485611 |
| N2AB | 13601 | 41026;41027;41028 | chr2:178620886;178620885;178620884 | chr2:179485613;179485612;179485611 |
| N2A | 12674 | 38245;38246;38247 | chr2:178620886;178620885;178620884 | chr2:179485613;179485612;179485611 |
| N2B | 6177 | 18754;18755;18756 | chr2:178620886;178620885;178620884 | chr2:179485613;179485612;179485611 |
| Novex-1 | 6302 | 19129;19130;19131 | chr2:178620886;178620885;178620884 | chr2:179485613;179485612;179485611 |
| Novex-2 | 6369 | 19330;19331;19332 | chr2:178620886;178620885;178620884 | chr2:179485613;179485612;179485611 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | rs373778707  |
-2.362 | 0.425 | N | 0.578 | 0.225 | None | gnomAD-2.1.1 | 2.51E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 5.51E-05 | 0 |
| R/G | rs373778707 |
-2.362 | 0.425 | N | 0.578 | 0.225 | None | gnomAD-3.1.2 | 4.61E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.03087E-04 | 0 | 0 |
| R/G | rs373778707 |
-2.362 | 0.425 | N | 0.578 | 0.225 | None | gnomAD-4.0.0 | 2.10851E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.88337E-05 | 0 | 0 |
| R/K | rs140795503 |
-1.51 | 0.001 | N | 0.144 | 0.103 | None | gnomAD-2.1.1 | 9.7E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.3468E-03 | None | 0 | None | 0 | 0 | 0 |
| R/K | rs140795503 |
-1.51 | 0.001 | N | 0.144 | 0.103 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 0 | 6.57E-05 | 0 | 0 | 7.80031E-04 | None | 0 | 0 | 0 | 0 | 0 |
| R/K | rs140795503 |
-1.51 | 0.001 | N | 0.144 | 0.103 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| R/K | rs140795503 |
-1.51 | 0.001 | N | 0.144 | 0.103 | None | gnomAD-4.0.0 | 6.57351E-05 | None | None | None | None | N | None | 0 | 1.67029E-05 | None | 0 | 2.32766E-03 | None | 0 | 0 | 8.48083E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.6745 | likely_pathogenic | 0.6755 | pathogenic | -1.45 | Destabilizing | 0.495 | N | 0.463 | neutral | None | None | None | None | N |
| R/C | 0.2372 | likely_benign | 0.221 | benign | -1.367 | Destabilizing | 0.995 | D | 0.673 | neutral | None | None | None | None | N |
| R/D | 0.9401 | likely_pathogenic | 0.9311 | pathogenic | -0.471 | Destabilizing | 0.704 | D | 0.588 | neutral | None | None | None | None | N |
| R/E | 0.6467 | likely_pathogenic | 0.6155 | pathogenic | -0.275 | Destabilizing | 0.329 | N | 0.367 | neutral | None | None | None | None | N |
| R/F | 0.7294 | likely_pathogenic | 0.7329 | pathogenic | -0.971 | Destabilizing | 0.981 | D | 0.679 | prob.neutral | None | None | None | None | N |
| R/G | 0.5656 | likely_pathogenic | 0.5581 | ambiguous | -1.817 | Destabilizing | 0.425 | N | 0.578 | neutral | N | 0.447900231 | None | None | N |
| R/H | 0.1655 | likely_benign | 0.1595 | benign | -2.008 | Highly Destabilizing | 0.944 | D | 0.603 | neutral | None | None | None | None | N |
| R/I | 0.3938 | ambiguous | 0.3932 | ambiguous | -0.419 | Destabilizing | 0.927 | D | 0.683 | prob.neutral | N | 0.445061464 | None | None | N |
| R/K | 0.0922 | likely_benign | 0.107 | benign | -1.068 | Destabilizing | 0.001 | N | 0.144 | neutral | N | 0.328711299 | None | None | N |
| R/L | 0.3878 | ambiguous | 0.3889 | ambiguous | -0.419 | Destabilizing | 0.495 | N | 0.578 | neutral | None | None | None | None | N |
| R/M | 0.441 | ambiguous | 0.4589 | ambiguous | -0.824 | Destabilizing | 0.981 | D | 0.65 | neutral | None | None | None | None | N |
| R/N | 0.8446 | likely_pathogenic | 0.8474 | pathogenic | -0.9 | Destabilizing | 0.704 | D | 0.537 | neutral | None | None | None | None | N |
| R/P | 0.9598 | likely_pathogenic | 0.9527 | pathogenic | -0.745 | Destabilizing | 0.828 | D | 0.633 | neutral | None | None | None | None | N |
| R/Q | 0.1451 | likely_benign | 0.1396 | benign | -0.894 | Destabilizing | 0.085 | N | 0.176 | neutral | None | None | None | None | N |
| R/S | 0.7612 | likely_pathogenic | 0.7563 | pathogenic | -1.779 | Destabilizing | 0.425 | N | 0.535 | neutral | N | 0.458494812 | None | None | N |
| R/T | 0.6025 | likely_pathogenic | 0.5903 | pathogenic | -1.356 | Destabilizing | 0.642 | D | 0.598 | neutral | N | 0.446985742 | None | None | N |
| R/V | 0.5522 | ambiguous | 0.5477 | ambiguous | -0.745 | Destabilizing | 0.828 | D | 0.612 | neutral | None | None | None | None | N |
| R/W | 0.2827 | likely_benign | 0.2869 | benign | -0.513 | Destabilizing | 0.995 | D | 0.693 | prob.neutral | None | None | None | None | N |
| R/Y | 0.5951 | likely_pathogenic | 0.5899 | pathogenic | -0.322 | Destabilizing | 0.981 | D | 0.666 | 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.