Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26445 | 79558;79559;79560 | chr2:178566799;178566798;178566797 | chr2:179431526;179431525;179431524 |
| N2AB | 24804 | 74635;74636;74637 | chr2:178566799;178566798;178566797 | chr2:179431526;179431525;179431524 |
| N2A | 23877 | 71854;71855;71856 | chr2:178566799;178566798;178566797 | chr2:179431526;179431525;179431524 |
| N2B | 17380 | 52363;52364;52365 | chr2:178566799;178566798;178566797 | chr2:179431526;179431525;179431524 |
| Novex-1 | 17505 | 52738;52739;52740 | chr2:178566799;178566798;178566797 | chr2:179431526;179431525;179431524 |
| Novex-2 | 17572 | 52939;52940;52941 | chr2:178566799;178566798;178566797 | chr2:179431526;179431525;179431524 |
| 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/C | rs780658084  |
-0.668 | 1.0 | N | 0.777 | 0.384 | None | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| R/C | rs780658084 |
-0.668 | 1.0 | N | 0.777 | 0.384 | None | gnomAD-4.0.0 | 7.52881E-06 | None | None | None | None | N | None | 0 | 4.47327E-05 | None | 0 | 0 | None | 1.88416E-05 | 0 | 1.79907E-06 | 3.47834E-05 | 4.97117E-05 |
| R/H | rs764254441 |
-1.446 | 1.0 | N | 0.771 | 0.342 | None | gnomAD-2.1.1 | 5.01E-05 | None | None | None | None | N | None | 8.27E-05 | 5.66E-05 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 7.05E-05 | 0 |
| R/H | rs764254441 |
-1.446 | 1.0 | N | 0.771 | 0.342 | None | gnomAD-3.1.2 | 8.55E-05 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 1.93874E-04 | None | 0 | 0 | 1.61774E-04 | 0 | 0 |
| R/H | rs764254441 |
-1.446 | 1.0 | N | 0.771 | 0.342 | None | gnomAD-4.0.0 | 7.19055E-05 | None | None | None | None | N | None | 4.00502E-05 | 5.00283E-05 | None | 0 | 8.92817E-05 | None | 0 | 1.64474E-04 | 8.05303E-05 | 6.58747E-05 | 6.40594E-05 |
| R/L | None | None | 1.0 | N | 0.658 | 0.386 | 0.674874776785 | gnomAD-4.0.0 | 6.84406E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99536E-07 | 0 | 0 |
| R/S | rs780658084 |
-1.025 | 1.0 | N | 0.732 | 0.268 | 0.379193981924 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| R/S | rs780658084 |
-1.025 | 1.0 | N | 0.732 | 0.268 | 0.379193981924 | gnomAD-4.0.0 | 6.84437E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99533E-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 | 0.9733 | likely_pathogenic | 0.9832 | pathogenic | -0.273 | Destabilizing | 0.999 | D | 0.607 | neutral | None | None | None | None | N |
| R/C | 0.6118 | likely_pathogenic | 0.7134 | pathogenic | -0.352 | Destabilizing | 1.0 | D | 0.777 | deleterious | N | 0.486741242 | None | None | N |
| R/D | 0.992 | likely_pathogenic | 0.995 | pathogenic | 0.034 | Stabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| R/E | 0.9601 | likely_pathogenic | 0.9734 | pathogenic | 0.153 | Stabilizing | 0.999 | D | 0.657 | neutral | None | None | None | None | N |
| R/F | 0.9574 | likely_pathogenic | 0.9721 | pathogenic | -0.193 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| R/G | 0.9436 | likely_pathogenic | 0.9664 | pathogenic | -0.559 | Destabilizing | 1.0 | D | 0.658 | neutral | N | 0.492221744 | None | None | N |
| R/H | 0.4146 | ambiguous | 0.5451 | ambiguous | -1.015 | Destabilizing | 1.0 | D | 0.771 | deleterious | N | 0.51775087 | None | None | N |
| R/I | 0.9319 | likely_pathogenic | 0.9591 | pathogenic | 0.476 | Stabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | N |
| R/K | 0.5741 | likely_pathogenic | 0.6852 | pathogenic | -0.302 | Destabilizing | 0.998 | D | 0.523 | neutral | None | None | None | None | N |
| R/L | 0.8697 | likely_pathogenic | 0.9239 | pathogenic | 0.476 | Stabilizing | 1.0 | D | 0.658 | neutral | N | 0.497501663 | None | None | N |
| R/M | 0.9373 | likely_pathogenic | 0.9662 | pathogenic | -0.048 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | N |
| R/N | 0.9753 | likely_pathogenic | 0.9838 | pathogenic | -0.007 | Destabilizing | 1.0 | D | 0.748 | deleterious | None | None | None | None | N |
| R/P | 0.9924 | likely_pathogenic | 0.9957 | pathogenic | 0.249 | Stabilizing | 1.0 | D | 0.731 | prob.delet. | N | 0.484575195 | None | None | N |
| R/Q | 0.5014 | ambiguous | 0.6467 | pathogenic | -0.07 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| R/S | 0.9656 | likely_pathogenic | 0.9785 | pathogenic | -0.54 | Destabilizing | 1.0 | D | 0.732 | prob.delet. | N | 0.491329486 | None | None | N |
| R/T | 0.9216 | likely_pathogenic | 0.955 | pathogenic | -0.246 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| R/V | 0.9396 | likely_pathogenic | 0.9623 | pathogenic | 0.249 | Stabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | N |
| R/W | 0.6492 | likely_pathogenic | 0.7634 | pathogenic | -0.051 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | N |
| R/Y | 0.8675 | likely_pathogenic | 0.9157 | pathogenic | 0.298 | Stabilizing | 1.0 | D | 0.762 | deleterious | 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.