Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13881 | 41866;41867;41868 | chr2:178635683;178635682;178635681 | chr2:179500410;179500409;179500408 |
| N2AB | 12240 | 36943;36944;36945 | chr2:178635683;178635682;178635681 | chr2:179500410;179500409;179500408 |
| N2A | 11313 | 34162;34163;34164 | chr2:178635683;178635682;178635681 | chr2:179500410;179500409;179500408 |
| N2B | 4816 | 14671;14672;14673 | chr2:178635683;178635682;178635681 | chr2:179500410;179500409;179500408 |
| Novex-1 | 4941 | 15046;15047;15048 | chr2:178635683;178635682;178635681 | chr2:179500410;179500409;179500408 |
| Novex-2 | 5008 | 15247;15248;15249 | chr2:178635683;178635682;178635681 | chr2:179500410;179500409;179500408 |
| 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/G | rs747469275  |
-0.979 | 0.983 | N | 0.636 | 0.226 | 0.363158594168 | gnomAD-2.1.1 | 8.71E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.95E-05 | 0 |
| R/G | rs747469275 |
-0.979 | 0.983 | N | 0.636 | 0.226 | 0.363158594168 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| R/G | rs747469275 |
-0.979 | 0.983 | N | 0.636 | 0.226 | 0.363158594168 | gnomAD-4.0.0 | 2.08244E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.64217E-05 | 0 | 2.87969E-05 |
| R/L | None | None | 0.992 | N | 0.685 | 0.299 | 0.379881503574 | gnomAD-4.0.0 | 6.89825E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.04295E-07 | 0 | 0 |
| R/Q | rs1268138413 |
0.041 | 0.998 | N | 0.613 | 0.254 | 0.211220785272 | gnomAD-2.1.1 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | None | 1.04406E-04 | 0 | None | 7.1E-05 | None | 0 | 0 | 0 |
| R/Q | rs1268138413 |
0.041 | 0.998 | N | 0.613 | 0.254 | 0.211220785272 | 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/Q | rs1268138413 |
0.041 | 0.998 | N | 0.613 | 0.254 | 0.211220785272 | gnomAD-4.0.0 | 6.24394E-06 | None | None | None | None | N | None | 2.67867E-05 | 0 | None | 3.41553E-05 | 0 | None | 0 | 0 | 3.40765E-06 | 3.3692E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.8212 | likely_pathogenic | 0.9015 | pathogenic | 0.11 | Stabilizing | 0.863 | D | 0.695 | prob.delet. | None | None | None | None | N |
| R/C | 0.5043 | ambiguous | 0.6691 | pathogenic | -0.036 | Destabilizing | 1.0 | D | 0.68 | prob.neutral | None | None | None | None | N |
| R/D | 0.9542 | likely_pathogenic | 0.9774 | pathogenic | -0.123 | Destabilizing | 0.991 | D | 0.691 | prob.delet. | None | None | None | None | N |
| R/E | 0.7506 | likely_pathogenic | 0.8499 | pathogenic | -0.05 | Destabilizing | 0.968 | D | 0.615 | neutral | None | None | None | None | N |
| R/F | 0.8879 | likely_pathogenic | 0.9408 | pathogenic | -0.058 | Destabilizing | 0.998 | D | 0.697 | prob.delet. | None | None | None | None | N |
| R/G | 0.6974 | likely_pathogenic | 0.8146 | pathogenic | -0.095 | Destabilizing | 0.983 | D | 0.636 | neutral | N | 0.499180298 | None | None | N |
| R/H | 0.2616 | likely_benign | 0.3714 | ambiguous | -0.68 | Destabilizing | 0.998 | D | 0.601 | neutral | None | None | None | None | N |
| R/I | 0.6964 | likely_pathogenic | 0.8142 | pathogenic | 0.616 | Stabilizing | 0.995 | D | 0.715 | prob.delet. | None | None | None | None | N |
| R/K | 0.22 | likely_benign | 0.288 | benign | 0.017 | Stabilizing | 0.29 | N | 0.226 | neutral | None | None | None | None | N |
| R/L | 0.6549 | likely_pathogenic | 0.7757 | pathogenic | 0.616 | Stabilizing | 0.992 | D | 0.685 | prob.delet. | N | 0.502817686 | None | None | N |
| R/M | 0.733 | likely_pathogenic | 0.8457 | pathogenic | 0.085 | Stabilizing | 1.0 | D | 0.647 | neutral | None | None | None | None | N |
| R/N | 0.9216 | likely_pathogenic | 0.9595 | pathogenic | 0.2 | Stabilizing | 0.968 | D | 0.613 | neutral | None | None | None | None | N |
| R/P | 0.9264 | likely_pathogenic | 0.9573 | pathogenic | 0.468 | Stabilizing | 0.998 | D | 0.728 | deleterious | N | 0.499180298 | None | None | N |
| R/Q | 0.2411 | likely_benign | 0.3422 | ambiguous | 0.151 | Stabilizing | 0.998 | D | 0.613 | neutral | N | 0.426192035 | None | None | N |
| R/S | 0.873 | likely_pathogenic | 0.9305 | pathogenic | -0.058 | Destabilizing | 0.543 | D | 0.407 | neutral | None | None | None | None | N |
| R/T | 0.6869 | likely_pathogenic | 0.8217 | pathogenic | 0.15 | Stabilizing | 0.939 | D | 0.653 | prob.neutral | None | None | None | None | N |
| R/V | 0.7502 | likely_pathogenic | 0.8556 | pathogenic | 0.468 | Stabilizing | 0.995 | D | 0.682 | prob.neutral | None | None | None | None | N |
| R/W | 0.4551 | ambiguous | 0.6027 | pathogenic | -0.15 | Destabilizing | 1.0 | D | 0.656 | prob.neutral | None | None | None | None | N |
| R/Y | 0.7963 | likely_pathogenic | 0.8851 | pathogenic | 0.259 | Stabilizing | 0.998 | D | 0.706 | 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.