Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3201 | 9826;9827;9828 | chr2:178766483;178766482;178766481 | chr2:179631210;179631209;179631208 |
| N2AB | 3201 | 9826;9827;9828 | chr2:178766483;178766482;178766481 | chr2:179631210;179631209;179631208 |
| N2A | 3201 | 9826;9827;9828 | chr2:178766483;178766482;178766481 | chr2:179631210;179631209;179631208 |
| N2B | 3155 | 9688;9689;9690 | chr2:178766483;178766482;178766481 | chr2:179631210;179631209;179631208 |
| Novex-1 | 3155 | 9688;9689;9690 | chr2:178766483;178766482;178766481 | chr2:179631210;179631209;179631208 |
| Novex-2 | 3155 | 9688;9689;9690 | chr2:178766483;178766482;178766481 | chr2:179631210;179631209;179631208 |
| Novex-3 | 3201 | 9826;9827;9828 | chr2:178766483;178766482;178766481 | chr2:179631210;179631209;179631208 |
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/K | rs2090450408  |
None | 0.061 | N | 0.171 | 0.208 | 0.348983352498 | gnomAD-4.0.0 | 1.59054E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.0217E-05 |
| R/S | rs1349281831 |
-0.743 | 0.92 | D | 0.428 | 0.353 | 0.451692371253 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 2.89E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/S | rs1349281831 |
-0.743 | 0.92 | D | 0.428 | 0.353 | 0.451692371253 | gnomAD-4.0.0 | 1.59055E-06 | None | None | None | None | N | None | 0 | 2.28645E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 | 0.9667 | likely_pathogenic | 0.9317 | pathogenic | -0.538 | Destabilizing | 0.863 | D | 0.405 | neutral | None | None | None | None | N |
| R/C | 0.8112 | likely_pathogenic | 0.6656 | pathogenic | -0.44 | Destabilizing | 0.999 | D | 0.523 | neutral | None | None | None | None | N |
| R/D | 0.9835 | likely_pathogenic | 0.9669 | pathogenic | -0.012 | Destabilizing | 0.969 | D | 0.484 | neutral | None | None | None | None | N |
| R/E | 0.9416 | likely_pathogenic | 0.9016 | pathogenic | 0.119 | Stabilizing | 0.863 | D | 0.36 | neutral | None | None | None | None | N |
| R/F | 0.9768 | likely_pathogenic | 0.9523 | pathogenic | -0.293 | Destabilizing | 0.991 | D | 0.513 | neutral | None | None | None | None | N |
| R/G | 0.8567 | likely_pathogenic | 0.724 | pathogenic | -0.868 | Destabilizing | 0.959 | D | 0.481 | neutral | N | 0.499943505 | None | None | N |
| R/H | 0.5092 | ambiguous | 0.3516 | ambiguous | -1.262 | Destabilizing | 0.1 | N | 0.205 | neutral | None | None | None | None | N |
| R/I | 0.9494 | likely_pathogenic | 0.9227 | pathogenic | 0.347 | Stabilizing | 0.996 | D | 0.517 | neutral | D | 0.578927745 | None | None | N |
| R/K | 0.3852 | ambiguous | 0.2816 | benign | -0.646 | Destabilizing | 0.061 | N | 0.171 | neutral | N | 0.464796463 | None | None | N |
| R/L | 0.8864 | likely_pathogenic | 0.8159 | pathogenic | 0.347 | Stabilizing | 0.969 | D | 0.471 | neutral | None | None | None | None | N |
| R/M | 0.9317 | likely_pathogenic | 0.8774 | pathogenic | -0.044 | Destabilizing | 0.997 | D | 0.458 | neutral | None | None | None | None | N |
| R/N | 0.9486 | likely_pathogenic | 0.8972 | pathogenic | -0.124 | Destabilizing | 0.939 | D | 0.367 | neutral | None | None | None | None | N |
| R/P | 0.9882 | likely_pathogenic | 0.9767 | pathogenic | 0.074 | Stabilizing | 0.997 | D | 0.483 | neutral | None | None | None | None | N |
| R/Q | 0.4857 | ambiguous | 0.3486 | ambiguous | -0.224 | Destabilizing | 0.939 | D | 0.442 | neutral | None | None | None | None | N |
| R/S | 0.9719 | likely_pathogenic | 0.9372 | pathogenic | -0.778 | Destabilizing | 0.92 | D | 0.428 | neutral | D | 0.532226132 | None | None | N |
| R/T | 0.941 | likely_pathogenic | 0.8791 | pathogenic | -0.464 | Destabilizing | 0.959 | D | 0.445 | neutral | N | 0.508584623 | None | None | N |
| R/V | 0.9592 | likely_pathogenic | 0.9335 | pathogenic | 0.074 | Stabilizing | 0.991 | D | 0.483 | neutral | None | None | None | None | N |
| R/W | 0.8068 | likely_pathogenic | 0.7172 | pathogenic | 0.001 | Stabilizing | 0.999 | D | 0.557 | neutral | None | None | None | None | N |
| R/Y | 0.9414 | likely_pathogenic | 0.8708 | pathogenic | 0.297 | Stabilizing | 0.982 | D | 0.503 | 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.