Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13835 | 41728;41729;41730 | chr2:178636068;178636067;178636066 | chr2:179500795;179500794;179500793 |
| N2AB | 12194 | 36805;36806;36807 | chr2:178636068;178636067;178636066 | chr2:179500795;179500794;179500793 |
| N2A | 11267 | 34024;34025;34026 | chr2:178636068;178636067;178636066 | chr2:179500795;179500794;179500793 |
| N2B | 4770 | 14533;14534;14535 | chr2:178636068;178636067;178636066 | chr2:179500795;179500794;179500793 |
| Novex-1 | 4895 | 14908;14909;14910 | chr2:178636068;178636067;178636066 | chr2:179500795;179500794;179500793 |
| Novex-2 | 4962 | 15109;15110;15111 | chr2:178636068;178636067;178636066 | chr2:179500795;179500794;179500793 |
| 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 | rs727504539  |
-1.314 | 0.271 | N | 0.679 | 0.077 | 0.0716867268079 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| R/Q | rs727504539 |
-1.314 | 0.271 | N | 0.679 | 0.077 | 0.0716867268079 | gnomAD-4.0.0 | 1.09506E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.2595E-05 | 1.15977E-05 | 1.657E-05 |
| R/W | rs886055278 |
None | 0.984 | N | 0.767 | 0.185 | 0.181679512989 | gnomAD-4.0.0 | 1.36882E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79929E-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 | 0.9079 | likely_pathogenic | 0.9355 | pathogenic | -1.437 | Destabilizing | 0.035 | N | 0.668 | prob.neutral | None | None | None | None | N |
| R/C | 0.4746 | ambiguous | 0.4794 | ambiguous | -1.443 | Destabilizing | 0.935 | D | 0.762 | deleterious | None | None | None | None | N |
| R/D | 0.9795 | likely_pathogenic | 0.984 | pathogenic | -0.523 | Destabilizing | 0.149 | N | 0.719 | prob.delet. | None | None | None | None | N |
| R/E | 0.8643 | likely_pathogenic | 0.8881 | pathogenic | -0.339 | Destabilizing | 0.035 | N | 0.605 | neutral | None | None | None | None | N |
| R/F | 0.9357 | likely_pathogenic | 0.9459 | pathogenic | -0.916 | Destabilizing | 0.555 | D | 0.775 | deleterious | None | None | None | None | N |
| R/G | 0.8324 | likely_pathogenic | 0.8628 | pathogenic | -1.801 | Destabilizing | 0.251 | N | 0.687 | prob.delet. | N | 0.338988895 | None | None | N |
| R/H | 0.1931 | likely_benign | 0.2045 | benign | -1.731 | Destabilizing | None | N | 0.183 | neutral | None | None | None | None | N |
| R/I | 0.8662 | likely_pathogenic | 0.8906 | pathogenic | -0.412 | Destabilizing | 0.555 | D | 0.794 | deleterious | None | None | None | None | N |
| R/K | 0.2453 | likely_benign | 0.3919 | ambiguous | -1.19 | Destabilizing | None | N | 0.227 | neutral | None | None | None | None | N |
| R/L | 0.7522 | likely_pathogenic | 0.7748 | pathogenic | -0.412 | Destabilizing | 0.251 | N | 0.717 | prob.delet. | N | 0.330967845 | None | None | N |
| R/M | 0.8355 | likely_pathogenic | 0.8703 | pathogenic | -0.797 | Destabilizing | 0.791 | D | 0.698 | prob.delet. | None | None | None | None | N |
| R/N | 0.9343 | likely_pathogenic | 0.949 | pathogenic | -0.914 | Destabilizing | 0.149 | N | 0.676 | prob.neutral | None | None | None | None | N |
| R/P | 0.9852 | likely_pathogenic | 0.9882 | pathogenic | -0.737 | Destabilizing | 0.705 | D | 0.751 | deleterious | N | 0.417670647 | None | None | N |
| R/Q | 0.3205 | likely_benign | 0.3575 | ambiguous | -0.932 | Destabilizing | 0.271 | N | 0.679 | prob.neutral | N | 0.323597143 | None | None | N |
| R/S | 0.9309 | likely_pathogenic | 0.9479 | pathogenic | -1.815 | Destabilizing | 0.081 | N | 0.727 | deleterious | None | None | None | None | N |
| R/T | 0.8413 | likely_pathogenic | 0.8832 | pathogenic | -1.417 | Destabilizing | 0.149 | N | 0.738 | deleterious | None | None | None | None | N |
| R/V | 0.8694 | likely_pathogenic | 0.8914 | pathogenic | -0.737 | Destabilizing | 0.38 | N | 0.751 | deleterious | None | None | None | None | N |
| R/W | 0.5149 | ambiguous | 0.5063 | ambiguous | -0.437 | Destabilizing | 0.984 | D | 0.767 | deleterious | N | 0.382647474 | None | None | N |
| R/Y | 0.762 | likely_pathogenic | 0.7664 | pathogenic | -0.203 | Destabilizing | 0.38 | N | 0.745 | 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.