Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20488 | 61687;61688;61689 | chr2:178590263;178590262;178590261 | chr2:179454990;179454989;179454988 |
| N2AB | 18847 | 56764;56765;56766 | chr2:178590263;178590262;178590261 | chr2:179454990;179454989;179454988 |
| N2A | 17920 | 53983;53984;53985 | chr2:178590263;178590262;178590261 | chr2:179454990;179454989;179454988 |
| N2B | 11423 | 34492;34493;34494 | chr2:178590263;178590262;178590261 | chr2:179454990;179454989;179454988 |
| Novex-1 | 11548 | 34867;34868;34869 | chr2:178590263;178590262;178590261 | chr2:179454990;179454989;179454988 |
| Novex-2 | 11615 | 35068;35069;35070 | chr2:178590263;178590262;178590261 | chr2:179454990;179454989;179454988 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs778745953  |
-1.875 | 0.999 | D | 0.501 | 0.584 | 0.754719756649 | gnomAD-2.1.1 | 4.58E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.76E-05 | None | 0 | None | 0 | 0 | 0 |
| V/A | rs778745953 |
-1.875 | 0.999 | D | 0.501 | 0.584 | 0.754719756649 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 1.94024E-04 | None | 0 | 0 | 0 | 0 | 0 |
| V/A | rs778745953 |
-1.875 | 0.999 | D | 0.501 | 0.584 | 0.754719756649 | gnomAD-4.0.0 | 2.6823E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 4.89165E-05 | None | 0 | 0 | 0 | 0 | 0 |
| V/L | None | None | 0.999 | N | 0.518 | 0.444 | 0.728599915167 | gnomAD-4.0.0 | 7.00948E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.13314E-07 | 0 | 0 |
| V/M | rs77957535 |
-0.798 | 1.0 | D | 0.746 | 0.486 | None | gnomAD-2.1.1 | 2.74E-05 | None | None | None | None | I | None | 0 | 3.23E-05 | None | 0 | 5.76E-05 | None | 1.34096E-04 | None | 5.15E-05 | 0 | 0 |
| V/M | rs77957535 |
-0.798 | 1.0 | D | 0.746 | 0.486 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 3.87597E-04 | None | 0 | 0 | 1.47E-05 | 0 | 4.78011E-04 |
| V/M | rs77957535 |
-0.798 | 1.0 | D | 0.746 | 0.486 | None | gnomAD-4.0.0 | 1.39352E-05 | None | None | None | None | I | None | 0 | 5.30279E-05 | None | 0 | 8.98473E-05 | None | 1.60036E-05 | 0 | 7.73951E-06 | 3.58551E-05 | 3.28364E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.6431 | likely_pathogenic | 0.6768 | pathogenic | -1.866 | Destabilizing | 0.999 | D | 0.501 | neutral | D | 0.535947921 | None | None | I |
| V/C | 0.8737 | likely_pathogenic | 0.8864 | pathogenic | -1.352 | Destabilizing | 1.0 | D | 0.661 | neutral | None | None | None | None | I |
| V/D | 0.9889 | likely_pathogenic | 0.9898 | pathogenic | -1.95 | Destabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | I |
| V/E | 0.9538 | likely_pathogenic | 0.959 | pathogenic | -1.874 | Destabilizing | 1.0 | D | 0.684 | prob.neutral | D | 0.534852031 | None | None | I |
| V/F | 0.5529 | ambiguous | 0.6429 | pathogenic | -1.286 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | I |
| V/G | 0.8556 | likely_pathogenic | 0.8543 | pathogenic | -2.27 | Highly Destabilizing | 1.0 | D | 0.708 | prob.delet. | D | 0.523077652 | None | None | I |
| V/H | 0.9755 | likely_pathogenic | 0.9808 | pathogenic | -1.834 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | I |
| V/I | 0.1035 | likely_benign | 0.1184 | benign | -0.807 | Destabilizing | 0.998 | D | 0.469 | neutral | None | None | None | None | I |
| V/K | 0.95 | likely_pathogenic | 0.953 | pathogenic | -1.511 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | I |
| V/L | 0.549 | ambiguous | 0.6022 | pathogenic | -0.807 | Destabilizing | 0.999 | D | 0.518 | neutral | N | 0.495601647 | None | None | I |
| V/M | 0.4503 | ambiguous | 0.4689 | ambiguous | -0.696 | Destabilizing | 1.0 | D | 0.746 | deleterious | D | 0.527597102 | None | None | I |
| V/N | 0.9593 | likely_pathogenic | 0.9641 | pathogenic | -1.454 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | I |
| V/P | 0.9941 | likely_pathogenic | 0.9939 | pathogenic | -1.128 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | I |
| V/Q | 0.9252 | likely_pathogenic | 0.9319 | pathogenic | -1.535 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | I |
| V/R | 0.9302 | likely_pathogenic | 0.9332 | pathogenic | -1.086 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | I |
| V/S | 0.8503 | likely_pathogenic | 0.8655 | pathogenic | -2.051 | Highly Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | I |
| V/T | 0.6677 | likely_pathogenic | 0.699 | pathogenic | -1.858 | Destabilizing | 0.999 | D | 0.639 | neutral | None | None | None | None | I |
| V/W | 0.9883 | likely_pathogenic | 0.9918 | pathogenic | -1.587 | Destabilizing | 1.0 | D | 0.653 | neutral | None | None | None | None | I |
| V/Y | 0.9192 | likely_pathogenic | 0.9443 | pathogenic | -1.276 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | 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.