Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18530 | 55813;55814;55815 | chr2:178601409;178601408;178601407 | chr2:179466136;179466135;179466134 |
| N2AB | 16889 | 50890;50891;50892 | chr2:178601409;178601408;178601407 | chr2:179466136;179466135;179466134 |
| N2A | 15962 | 48109;48110;48111 | chr2:178601409;178601408;178601407 | chr2:179466136;179466135;179466134 |
| N2B | 9465 | 28618;28619;28620 | chr2:178601409;178601408;178601407 | chr2:179466136;179466135;179466134 |
| Novex-1 | 9590 | 28993;28994;28995 | chr2:178601409;178601408;178601407 | chr2:179466136;179466135;179466134 |
| Novex-2 | 9657 | 29194;29195;29196 | chr2:178601409;178601408;178601407 | chr2:179466136;179466135;179466134 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/I | None | None | 0.968 | N | 0.739 | 0.363 | 0.483374165343 | gnomAD-4.0.0 | 1.59334E-06 | None | None | None | None | N | None | 5.66829E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| N/S | rs749840185  |
-0.924 | 0.251 | N | 0.393 | 0.111 | 0.15556083564 | 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 |
| N/S | rs749840185 |
-0.924 | 0.251 | N | 0.393 | 0.111 | 0.15556083564 | gnomAD-4.0.0 | 4.78002E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.72328E-06 | 0 | 3.02773E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.253 | likely_benign | 0.3111 | benign | -0.816 | Destabilizing | 0.851 | D | 0.639 | neutral | None | None | None | None | N |
| N/C | 0.1972 | likely_benign | 0.2169 | benign | 0.003 | Stabilizing | 0.999 | D | 0.729 | prob.delet. | None | None | None | None | N |
| N/D | 0.2832 | likely_benign | 0.3742 | ambiguous | -0.446 | Destabilizing | 0.896 | D | 0.605 | neutral | N | 0.487678679 | None | None | N |
| N/E | 0.6096 | likely_pathogenic | 0.6975 | pathogenic | -0.306 | Destabilizing | 0.919 | D | 0.661 | neutral | None | None | None | None | N |
| N/F | 0.5285 | ambiguous | 0.6101 | pathogenic | -0.565 | Destabilizing | 0.988 | D | 0.743 | deleterious | None | None | None | None | N |
| N/G | 0.433 | ambiguous | 0.5136 | ambiguous | -1.185 | Destabilizing | 0.919 | D | 0.603 | neutral | None | None | None | None | N |
| N/H | 0.1126 | likely_benign | 0.1414 | benign | -0.835 | Destabilizing | 0.995 | D | 0.682 | prob.neutral | N | 0.502552131 | None | None | N |
| N/I | 0.211 | likely_benign | 0.2572 | benign | 0.133 | Stabilizing | 0.968 | D | 0.739 | prob.delet. | N | 0.515865358 | None | None | N |
| N/K | 0.4483 | ambiguous | 0.5679 | pathogenic | -0.119 | Destabilizing | 0.896 | D | 0.655 | neutral | N | 0.511747617 | None | None | N |
| N/L | 0.2364 | likely_benign | 0.2725 | benign | 0.133 | Stabilizing | 0.851 | D | 0.683 | prob.neutral | None | None | None | None | N |
| N/M | 0.3066 | likely_benign | 0.3705 | ambiguous | 0.413 | Stabilizing | 0.999 | D | 0.697 | prob.neutral | None | None | None | None | N |
| N/P | 0.7773 | likely_pathogenic | 0.8139 | pathogenic | -0.153 | Destabilizing | 0.988 | D | 0.707 | prob.neutral | None | None | None | None | N |
| N/Q | 0.3838 | ambiguous | 0.4483 | ambiguous | -0.683 | Destabilizing | 0.988 | D | 0.711 | prob.delet. | None | None | None | None | N |
| N/R | 0.4629 | ambiguous | 0.5612 | ambiguous | -0.249 | Destabilizing | 0.988 | D | 0.699 | prob.neutral | None | None | None | None | N |
| N/S | 0.0879 | likely_benign | 0.0968 | benign | -0.889 | Destabilizing | 0.251 | N | 0.393 | neutral | N | 0.454699469 | None | None | N |
| N/T | 0.1238 | likely_benign | 0.1538 | benign | -0.537 | Destabilizing | 0.046 | N | 0.272 | neutral | N | 0.48084592 | None | None | N |
| N/V | 0.2197 | likely_benign | 0.2627 | benign | -0.153 | Destabilizing | 0.952 | D | 0.693 | prob.neutral | None | None | None | None | N |
| N/W | 0.7528 | likely_pathogenic | 0.8237 | pathogenic | -0.368 | Destabilizing | 0.999 | D | 0.697 | prob.neutral | None | None | None | None | N |
| N/Y | 0.1813 | likely_benign | 0.222 | benign | -0.111 | Destabilizing | 0.995 | D | 0.703 | prob.neutral | N | 0.491220417 | 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.