Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31757 | 95494;95495;95496 | chr2:178545967;178545966;178545965 | chr2:179410694;179410693;179410692 |
| N2AB | 30116 | 90571;90572;90573 | chr2:178545967;178545966;178545965 | chr2:179410694;179410693;179410692 |
| N2A | 29189 | 87790;87791;87792 | chr2:178545967;178545966;178545965 | chr2:179410694;179410693;179410692 |
| N2B | 22692 | 68299;68300;68301 | chr2:178545967;178545966;178545965 | chr2:179410694;179410693;179410692 |
| Novex-1 | 22817 | 68674;68675;68676 | chr2:178545967;178545966;178545965 | chr2:179410694;179410693;179410692 |
| Novex-2 | 22884 | 68875;68876;68877 | chr2:178545967;178545966;178545965 | chr2:179410694;179410693;179410692 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs72648259  |
-0.661 | 0.998 | N | 0.651 | 0.421 | None | gnomAD-2.1.1 | 3.89211E-04 | None | None | None | None | I | None | 1.23987E-04 | 3.11297E-04 | None | 3.86997E-04 | 0 | None | 3.92131E-04 | None | 0 | 5.62755E-04 | 9.82043E-04 |
| I/T | rs72648259 |
-0.661 | 0.998 | N | 0.651 | 0.421 | None | gnomAD-3.1.2 | 4.86311E-04 | None | None | None | None | I | None | 2.17171E-04 | 5.23903E-04 | 0 | 0 | 0 | None | 0 | 0 | 7.49625E-04 | 4.13736E-04 | 1.91388E-03 |
| I/T | rs72648259 |
-0.661 | 0.998 | N | 0.651 | 0.421 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | I | None | 0 | 1.4E-03 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| I/T | rs72648259 |
-0.661 | 0.998 | N | 0.651 | 0.421 | None | gnomAD-4.0.0 | 5.37846E-04 | None | None | None | None | I | None | 1.5994E-04 | 4.16639E-04 | None | 4.05433E-04 | 0 | None | 0 | 4.94886E-04 | 6.18747E-04 | 5.05006E-04 | 6.40225E-04 |
| I/V | None | None | 0.889 | N | 0.361 | 0.135 | 0.597732455086 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.2272 | likely_benign | 0.2147 | benign | -1.267 | Destabilizing | 0.996 | D | 0.589 | neutral | None | None | None | None | I |
| I/C | 0.6148 | likely_pathogenic | 0.6176 | pathogenic | -0.825 | Destabilizing | 1.0 | D | 0.69 | prob.neutral | None | None | None | None | I |
| I/D | 0.7295 | likely_pathogenic | 0.7075 | pathogenic | -0.805 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | I |
| I/E | 0.5911 | likely_pathogenic | 0.5755 | pathogenic | -0.847 | Destabilizing | 1.0 | D | 0.728 | prob.delet. | None | None | None | None | I |
| I/F | 0.2214 | likely_benign | 0.1988 | benign | -0.915 | Destabilizing | 0.997 | D | 0.637 | neutral | N | 0.502010626 | None | None | I |
| I/G | 0.6211 | likely_pathogenic | 0.5982 | pathogenic | -1.525 | Destabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | I |
| I/H | 0.5693 | likely_pathogenic | 0.5489 | ambiguous | -0.666 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | I |
| I/K | 0.4649 | ambiguous | 0.4705 | ambiguous | -0.935 | Destabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | I |
| I/L | 0.0914 | likely_benign | 0.0866 | benign | -0.664 | Destabilizing | 0.104 | N | 0.211 | neutral | N | 0.410524617 | None | None | I |
| I/M | 0.0834 | likely_benign | 0.079 | benign | -0.556 | Destabilizing | 0.997 | D | 0.655 | neutral | N | 0.490793555 | None | None | I |
| I/N | 0.3156 | likely_benign | 0.2828 | benign | -0.744 | Destabilizing | 0.999 | D | 0.721 | prob.delet. | N | 0.494601865 | None | None | I |
| I/P | 0.4906 | ambiguous | 0.5011 | ambiguous | -0.832 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | I |
| I/Q | 0.4333 | ambiguous | 0.4283 | ambiguous | -0.964 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | I |
| I/R | 0.3618 | ambiguous | 0.3734 | ambiguous | -0.266 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | I |
| I/S | 0.2798 | likely_benign | 0.2649 | benign | -1.264 | Destabilizing | 0.999 | D | 0.66 | neutral | N | 0.47120493 | None | None | I |
| I/T | 0.1476 | likely_benign | 0.1335 | benign | -1.197 | Destabilizing | 0.998 | D | 0.651 | neutral | N | 0.400363552 | None | None | I |
| I/V | 0.0802 | likely_benign | 0.0762 | benign | -0.832 | Destabilizing | 0.889 | D | 0.361 | neutral | N | 0.390455989 | None | None | I |
| I/W | 0.7511 | likely_pathogenic | 0.7629 | pathogenic | -0.943 | Destabilizing | 1.0 | D | 0.688 | prob.neutral | None | None | None | None | I |
| I/Y | 0.5634 | ambiguous | 0.5553 | ambiguous | -0.739 | Destabilizing | 1.0 | D | 0.725 | 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.