Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1479 | 4660;4661;4662 | chr2:178777749;178777748;178777747 | chr2:179642476;179642475;179642474 |
| N2AB | 1479 | 4660;4661;4662 | chr2:178777749;178777748;178777747 | chr2:179642476;179642475;179642474 |
| N2A | 1479 | 4660;4661;4662 | chr2:178777749;178777748;178777747 | chr2:179642476;179642475;179642474 |
| N2B | 1433 | 4522;4523;4524 | chr2:178777749;178777748;178777747 | chr2:179642476;179642475;179642474 |
| Novex-1 | 1433 | 4522;4523;4524 | chr2:178777749;178777748;178777747 | chr2:179642476;179642475;179642474 |
| Novex-2 | 1433 | 4522;4523;4524 | chr2:178777749;178777748;178777747 | chr2:179642476;179642475;179642474 |
| Novex-3 | 1479 | 4660;4661;4662 | chr2:178777749;178777748;178777747 | chr2:179642476;179642475;179642474 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/N | None | None | 1.0 | D | 0.758 | 0.403 | 0.17948927462 | gnomAD-4.0.0 | 2.73644E-06 | None | None | None | None | I | None | 8.96432E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65596E-05 |
| K/R | rs566441215  |
-0.553 | 0.999 | N | 0.509 | 0.428 | 0.341226946553 | gnomAD-2.1.1 | 7.97E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 6.53E-05 | None | 0 | 0 | 0 |
| K/R | rs566441215 |
-0.553 | 0.999 | N | 0.509 | 0.428 | 0.341226946553 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07125E-04 | 0 |
| K/R | rs566441215 |
-0.553 | 0.999 | N | 0.509 | 0.428 | 0.341226946553 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| K/R | rs566441215 |
-0.553 | 0.999 | N | 0.509 | 0.428 | 0.341226946553 | gnomAD-4.0.0 | 1.36299E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.52547E-05 | 4.39165E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.9663 | likely_pathogenic | 0.9757 | pathogenic | -0.721 | Destabilizing | 0.999 | D | 0.65 | neutral | None | None | None | None | I |
| K/C | 0.9793 | likely_pathogenic | 0.9851 | pathogenic | -0.902 | Destabilizing | 1.0 | D | 0.78 | deleterious | None | None | None | None | I |
| K/D | 0.9945 | likely_pathogenic | 0.996 | pathogenic | -0.393 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | I |
| K/E | 0.955 | likely_pathogenic | 0.9693 | pathogenic | -0.235 | Destabilizing | 0.999 | D | 0.575 | neutral | N | 0.509887104 | None | None | I |
| K/F | 0.9956 | likely_pathogenic | 0.997 | pathogenic | -0.28 | Destabilizing | 1.0 | D | 0.79 | deleterious | None | None | None | None | I |
| K/G | 0.9862 | likely_pathogenic | 0.9884 | pathogenic | -1.127 | Destabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | I |
| K/H | 0.8672 | likely_pathogenic | 0.8938 | pathogenic | -1.432 | Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | I |
| K/I | 0.9568 | likely_pathogenic | 0.9704 | pathogenic | 0.354 | Stabilizing | 1.0 | D | 0.8 | deleterious | None | None | None | None | I |
| K/L | 0.9182 | likely_pathogenic | 0.9395 | pathogenic | 0.354 | Stabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | I |
| K/M | 0.867 | likely_pathogenic | 0.9037 | pathogenic | 0.111 | Stabilizing | 1.0 | D | 0.762 | deleterious | D | 0.638541191 | None | None | I |
| K/N | 0.9799 | likely_pathogenic | 0.9851 | pathogenic | -0.85 | Destabilizing | 1.0 | D | 0.758 | deleterious | D | 0.545873227 | None | None | I |
| K/P | 0.9979 | likely_pathogenic | 0.9978 | pathogenic | 0.025 | Stabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | I |
| K/Q | 0.7172 | likely_pathogenic | 0.7804 | pathogenic | -0.821 | Destabilizing | 1.0 | D | 0.742 | deleterious | N | 0.511323835 | None | None | I |
| K/R | 0.2233 | likely_benign | 0.2448 | benign | -0.803 | Destabilizing | 0.999 | D | 0.509 | neutral | N | 0.482803464 | None | None | I |
| K/S | 0.9783 | likely_pathogenic | 0.9846 | pathogenic | -1.503 | Destabilizing | 0.999 | D | 0.619 | neutral | None | None | None | None | I |
| K/T | 0.8825 | likely_pathogenic | 0.9133 | pathogenic | -1.123 | Destabilizing | 1.0 | D | 0.764 | deleterious | N | 0.507929475 | None | None | I |
| K/V | 0.9331 | likely_pathogenic | 0.9526 | pathogenic | 0.025 | Stabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | I |
| K/W | 0.994 | likely_pathogenic | 0.9955 | pathogenic | -0.191 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | I |
| K/Y | 0.9852 | likely_pathogenic | 0.9886 | pathogenic | 0.13 | Stabilizing | 1.0 | D | 0.785 | deleterious | 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.