Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18037 | 54334;54335;54336 | chr2:178605068;178605067;178605066 | chr2:179469795;179469794;179469793 |
| N2AB | 16396 | 49411;49412;49413 | chr2:178605068;178605067;178605066 | chr2:179469795;179469794;179469793 |
| N2A | 15469 | 46630;46631;46632 | chr2:178605068;178605067;178605066 | chr2:179469795;179469794;179469793 |
| N2B | 8972 | 27139;27140;27141 | chr2:178605068;178605067;178605066 | chr2:179469795;179469794;179469793 |
| Novex-1 | 9097 | 27514;27515;27516 | chr2:178605068;178605067;178605066 | chr2:179469795;179469794;179469793 |
| Novex-2 | 9164 | 27715;27716;27717 | chr2:178605068;178605067;178605066 | chr2:179469795;179469794;179469793 |
| 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/Q | rs541688627  |
0.274 | 1.0 | N | 0.676 | 0.361 | 0.176091768786 | gnomAD-2.1.1 | 2.02E-05 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 6.55E-05 | None | 0 | 8.94E-06 | 1.66445E-04 |
| R/Q | rs541688627 |
0.274 | 1.0 | N | 0.676 | 0.361 | 0.176091768786 | gnomAD-3.1.2 | 6.58E-05 | None | None | None | None | N | None | 4.83E-05 | 5.25279E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs541688627 |
0.274 | 1.0 | N | 0.676 | 0.361 | 0.176091768786 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/Q | rs541688627 |
0.274 | 1.0 | N | 0.676 | 0.361 | 0.176091768786 | gnomAD-4.0.0 | 1.79846E-05 | None | None | None | None | N | None | 4.00427E-05 | 2.16898E-04 | None | 0 | 0 | None | 0 | 0 | 7.6332E-06 | 3.29801E-05 | 1.60185E-05 |
| R/W | rs201623791 |
-0.266 | 1.0 | N | 0.759 | 0.374 | None | gnomAD-2.1.1 | 5.73E-05 | None | None | None | None | N | None | 1.24213E-04 | 2.83E-05 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 8.64E-05 | 0 |
| R/W | rs201623791 |
-0.266 | 1.0 | N | 0.759 | 0.374 | None | gnomAD-3.1.2 | 7.9E-05 | None | None | None | None | N | None | 1.44949E-04 | 6.57E-05 | 0 | 0 | 0 | None | 0 | 0 | 7.36E-05 | 0 | 0 |
| R/W | rs201623791 |
-0.266 | 1.0 | N | 0.759 | 0.374 | None | gnomAD-4.0.0 | 1.10395E-04 | None | None | None | None | N | None | 9.35954E-05 | 5.00734E-05 | None | 0 | 0 | None | 0 | 0 | 1.34002E-04 | 1.09914E-05 | 1.44231E-04 |
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 | 0.9706 | likely_pathogenic | 0.9725 | pathogenic | -0.208 | Destabilizing | 0.999 | D | 0.573 | neutral | None | None | None | None | N |
| R/C | 0.8819 | likely_pathogenic | 0.8912 | pathogenic | -0.214 | Destabilizing | 1.0 | D | 0.744 | deleterious | None | None | None | None | N |
| R/D | 0.9927 | likely_pathogenic | 0.9929 | pathogenic | 0.029 | Stabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | N |
| R/E | 0.9447 | likely_pathogenic | 0.9386 | pathogenic | 0.13 | Stabilizing | 0.999 | D | 0.615 | neutral | None | None | None | None | N |
| R/F | 0.986 | likely_pathogenic | 0.9877 | pathogenic | -0.156 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| R/G | 0.9656 | likely_pathogenic | 0.9659 | pathogenic | -0.48 | Destabilizing | 1.0 | D | 0.566 | neutral | N | 0.463467248 | None | None | N |
| R/H | 0.7581 | likely_pathogenic | 0.7558 | pathogenic | -0.925 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| R/I | 0.9302 | likely_pathogenic | 0.9279 | pathogenic | 0.499 | Stabilizing | 1.0 | D | 0.726 | prob.delet. | None | None | None | None | N |
| R/K | 0.4766 | ambiguous | 0.4717 | ambiguous | -0.286 | Destabilizing | 0.998 | D | 0.51 | neutral | None | None | None | None | N |
| R/L | 0.8832 | likely_pathogenic | 0.8811 | pathogenic | 0.499 | Stabilizing | 1.0 | D | 0.566 | neutral | N | 0.48668331 | None | None | N |
| R/M | 0.9546 | likely_pathogenic | 0.953 | pathogenic | 0.042 | Stabilizing | 1.0 | D | 0.714 | prob.delet. | None | None | None | None | N |
| R/N | 0.9889 | likely_pathogenic | 0.9901 | pathogenic | 0.121 | Stabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | N |
| R/P | 0.9598 | likely_pathogenic | 0.959 | pathogenic | 0.285 | Stabilizing | 1.0 | D | 0.679 | prob.neutral | N | 0.467713547 | None | None | N |
| R/Q | 0.6603 | likely_pathogenic | 0.6298 | pathogenic | 0.011 | Stabilizing | 1.0 | D | 0.676 | prob.neutral | N | 0.507888088 | None | None | N |
| R/S | 0.9886 | likely_pathogenic | 0.9892 | pathogenic | -0.388 | Destabilizing | 1.0 | D | 0.623 | neutral | None | None | None | None | N |
| R/T | 0.9667 | likely_pathogenic | 0.9688 | pathogenic | -0.126 | Destabilizing | 1.0 | D | 0.621 | neutral | None | None | None | None | N |
| R/V | 0.9548 | likely_pathogenic | 0.9559 | pathogenic | 0.285 | Stabilizing | 1.0 | D | 0.702 | prob.neutral | None | None | None | None | N |
| R/W | 0.8369 | likely_pathogenic | 0.8386 | pathogenic | -0.022 | Destabilizing | 1.0 | D | 0.759 | deleterious | N | 0.490472273 | None | None | N |
| R/Y | 0.97 | likely_pathogenic | 0.973 | pathogenic | 0.322 | Stabilizing | 1.0 | D | 0.702 | prob.neutral | 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.