Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23783 | 71572;71573;71574 | chr2:178574785;178574784;178574783 | chr2:179439512;179439511;179439510 |
| N2AB | 22142 | 66649;66650;66651 | chr2:178574785;178574784;178574783 | chr2:179439512;179439511;179439510 |
| N2A | 21215 | 63868;63869;63870 | chr2:178574785;178574784;178574783 | chr2:179439512;179439511;179439510 |
| N2B | 14718 | 44377;44378;44379 | chr2:178574785;178574784;178574783 | chr2:179439512;179439511;179439510 |
| Novex-1 | 14843 | 44752;44753;44754 | chr2:178574785;178574784;178574783 | chr2:179439512;179439511;179439510 |
| Novex-2 | 14910 | 44953;44954;44955 | chr2:178574785;178574784;178574783 | chr2:179439512;179439511;179439510 |
| 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 | rs754516257  |
-0.353 | 1.0 | N | 0.747 | 0.457 | None | gnomAD-2.1.1 | 8.11E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.61E-05 | None | 0 | None | 0 | 8.98E-06 | 0 |
| R/C | rs754516257 |
-0.353 | 1.0 | N | 0.747 | 0.457 | None | gnomAD-4.0.0 | 4.10991E-06 | None | None | None | None | N | None | 2.98972E-05 | 0 | None | 0 | 2.52781E-05 | None | 0 | 0 | 2.70074E-06 | 1.16214E-05 | 0 |
| R/H | rs145504744 |
-0.872 | 1.0 | N | 0.765 | 0.402 | None | gnomAD-2.1.1 | 4.32E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.63156E-04 | None | 0 | 7.89E-06 | 0 |
| R/H | rs145504744 |
-0.872 | 1.0 | N | 0.765 | 0.402 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/H | rs145504744 |
-0.872 | 1.0 | N | 0.765 | 0.402 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| R/H | rs145504744 |
-0.872 | 1.0 | N | 0.765 | 0.402 | None | gnomAD-4.0.0 | 3.28931E-05 | None | None | None | None | N | None | 1.33376E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.35796E-05 | 3.85556E-04 | 1.6039E-05 |
| R/P | rs145504744 |
None | 1.0 | N | 0.697 | 0.501 | 0.514587094315 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/P | rs145504744 |
None | 1.0 | N | 0.697 | 0.501 | 0.514587094315 | gnomAD-4.0.0 | 6.57635E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47076E-05 | 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 | 0.9758 | likely_pathogenic | 0.9759 | pathogenic | 0.069 | Stabilizing | 0.999 | D | 0.627 | neutral | None | None | None | None | N |
| R/C | 0.7628 | likely_pathogenic | 0.7761 | pathogenic | -0.225 | Destabilizing | 1.0 | D | 0.747 | deleterious | N | 0.471964669 | None | None | N |
| R/D | 0.9864 | likely_pathogenic | 0.9856 | pathogenic | -0.187 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| R/E | 0.9536 | likely_pathogenic | 0.9534 | pathogenic | -0.133 | Destabilizing | 0.999 | D | 0.665 | neutral | None | None | None | None | N |
| R/F | 0.9837 | likely_pathogenic | 0.9839 | pathogenic | -0.21 | Destabilizing | 1.0 | D | 0.718 | prob.delet. | None | None | None | None | N |
| R/G | 0.9135 | likely_pathogenic | 0.9009 | pathogenic | -0.094 | Destabilizing | 1.0 | D | 0.638 | neutral | N | 0.488697399 | None | None | N |
| R/H | 0.5622 | ambiguous | 0.5751 | pathogenic | -0.574 | Destabilizing | 1.0 | D | 0.765 | deleterious | N | 0.472507647 | None | None | N |
| R/I | 0.9699 | likely_pathogenic | 0.9779 | pathogenic | 0.457 | Stabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | N |
| R/K | 0.5129 | ambiguous | 0.5543 | ambiguous | -0.091 | Destabilizing | 0.998 | D | 0.525 | neutral | None | None | None | None | N |
| R/L | 0.9143 | likely_pathogenic | 0.9303 | pathogenic | 0.457 | Stabilizing | 1.0 | D | 0.638 | neutral | N | 0.521231105 | None | None | N |
| R/M | 0.9575 | likely_pathogenic | 0.9652 | pathogenic | -0.032 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| R/N | 0.979 | likely_pathogenic | 0.9787 | pathogenic | -0.009 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| R/P | 0.9904 | likely_pathogenic | 0.9904 | pathogenic | 0.347 | Stabilizing | 1.0 | D | 0.697 | prob.neutral | N | 0.476773608 | None | None | N |
| R/Q | 0.617 | likely_pathogenic | 0.6146 | pathogenic | -0.046 | Destabilizing | 1.0 | D | 0.736 | prob.delet. | None | None | None | None | N |
| R/S | 0.9744 | likely_pathogenic | 0.9717 | pathogenic | -0.239 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | N | 0.476632179 | None | None | N |
| R/T | 0.9589 | likely_pathogenic | 0.9666 | pathogenic | -0.065 | Destabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | N |
| R/V | 0.9725 | likely_pathogenic | 0.9773 | pathogenic | 0.347 | Stabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| R/W | 0.7911 | likely_pathogenic | 0.8063 | pathogenic | -0.359 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| R/Y | 0.9452 | likely_pathogenic | 0.9461 | pathogenic | 0.059 | Stabilizing | 1.0 | D | 0.727 | prob.delet. | 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.