Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30278 | 91057;91058;91059 | chr2:178552068;178552067;178552066 | chr2:179416795;179416794;179416793 |
| N2AB | 28637 | 86134;86135;86136 | chr2:178552068;178552067;178552066 | chr2:179416795;179416794;179416793 |
| N2A | 27710 | 83353;83354;83355 | chr2:178552068;178552067;178552066 | chr2:179416795;179416794;179416793 |
| N2B | 21213 | 63862;63863;63864 | chr2:178552068;178552067;178552066 | chr2:179416795;179416794;179416793 |
| Novex-1 | 21338 | 64237;64238;64239 | chr2:178552068;178552067;178552066 | chr2:179416795;179416794;179416793 |
| Novex-2 | 21405 | 64438;64439;64440 | chr2:178552068;178552067;178552066 | chr2:179416795;179416794;179416793 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/N | None | None | 0.999 | N | 0.555 | 0.25 | 0.248417906384 | gnomAD-4.0.0 | 6.15814E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 8.11764E-05 | 3.31323E-05 |
| S/R | rs397517751  |
0.176 | 1.0 | N | 0.692 | 0.464 | 0.263612267334 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| S/R | rs397517751 |
0.176 | 1.0 | N | 0.692 | 0.464 | 0.263612267334 | gnomAD-4.0.0 | 1.59138E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85834E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1461 | likely_benign | 0.1278 | benign | -0.408 | Destabilizing | 0.998 | D | 0.406 | neutral | None | None | None | None | I |
| S/C | 0.3167 | likely_benign | 0.2877 | benign | -0.24 | Destabilizing | 1.0 | D | 0.67 | neutral | N | 0.495339297 | None | None | I |
| S/D | 0.9404 | likely_pathogenic | 0.9066 | pathogenic | 0.026 | Stabilizing | 0.999 | D | 0.6 | neutral | None | None | None | None | I |
| S/E | 0.9492 | likely_pathogenic | 0.9339 | pathogenic | -0.085 | Destabilizing | 0.999 | D | 0.589 | neutral | None | None | None | None | I |
| S/F | 0.7488 | likely_pathogenic | 0.643 | pathogenic | -1.146 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | I |
| S/G | 0.2606 | likely_benign | 0.2029 | benign | -0.466 | Destabilizing | 0.999 | D | 0.453 | neutral | N | 0.481464783 | None | None | I |
| S/H | 0.8236 | likely_pathogenic | 0.7623 | pathogenic | -0.97 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | I |
| S/I | 0.7 | likely_pathogenic | 0.6302 | pathogenic | -0.383 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | D | 0.526045066 | None | None | I |
| S/K | 0.983 | likely_pathogenic | 0.9738 | pathogenic | -0.377 | Destabilizing | 0.999 | D | 0.593 | neutral | None | None | None | None | I |
| S/L | 0.3563 | ambiguous | 0.2815 | benign | -0.383 | Destabilizing | 1.0 | D | 0.675 | neutral | None | None | None | None | I |
| S/M | 0.5027 | ambiguous | 0.4066 | ambiguous | -0.053 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | I |
| S/N | 0.5652 | likely_pathogenic | 0.4267 | ambiguous | -0.088 | Destabilizing | 0.999 | D | 0.555 | neutral | N | 0.46043615 | None | None | I |
| S/P | 0.9181 | likely_pathogenic | 0.8971 | pathogenic | -0.367 | Destabilizing | 1.0 | D | 0.702 | prob.neutral | None | None | None | None | I |
| S/Q | 0.879 | likely_pathogenic | 0.8376 | pathogenic | -0.377 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | I |
| S/R | 0.9676 | likely_pathogenic | 0.9541 | pathogenic | -0.151 | Destabilizing | 1.0 | D | 0.692 | prob.neutral | N | 0.491508418 | None | None | I |
| S/T | 0.1994 | likely_benign | 0.1548 | benign | -0.207 | Destabilizing | 0.999 | D | 0.433 | neutral | N | 0.406062947 | None | None | I |
| S/V | 0.5746 | likely_pathogenic | 0.4986 | ambiguous | -0.367 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | I |
| S/W | 0.8248 | likely_pathogenic | 0.7995 | pathogenic | -1.157 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | I |
| S/Y | 0.6739 | likely_pathogenic | 0.5912 | pathogenic | -0.869 | Destabilizing | 1.0 | D | 0.742 | deleterious | None | None | None | None | I |
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.