Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22779 | 68560;68561;68562 | chr2:178578180;178578179;178578178 | chr2:179442907;179442906;179442905 |
| N2AB | 21138 | 63637;63638;63639 | chr2:178578180;178578179;178578178 | chr2:179442907;179442906;179442905 |
| N2A | 20211 | 60856;60857;60858 | chr2:178578180;178578179;178578178 | chr2:179442907;179442906;179442905 |
| N2B | 13714 | 41365;41366;41367 | chr2:178578180;178578179;178578178 | chr2:179442907;179442906;179442905 |
| Novex-1 | 13839 | 41740;41741;41742 | chr2:178578180;178578179;178578178 | chr2:179442907;179442906;179442905 |
| Novex-2 | 13906 | 41941;41942;41943 | chr2:178578180;178578179;178578178 | chr2:179442907;179442906;179442905 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/N | rs727504702  |
-2.1 | 0.931 | N | 0.598 | 0.326 | 0.284539287134 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.95E-05 | 0 | 0 |
| H/N | rs727504702 |
-2.1 | 0.931 | N | 0.598 | 0.326 | 0.284539287134 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| H/N | rs727504702 |
-2.1 | 0.931 | N | 0.598 | 0.326 | 0.284539287134 | gnomAD-4.0.0 | 3.85763E-06 | None | None | None | None | N | None | 1.69411E-05 | 0 | None | 0 | 0 | None | 1.60948E-05 | 0 | 2.3964E-06 | 0 | 0 |
| H/R | rs2046870032 |
None | 0.939 | N | 0.591 | 0.398 | 0.290222751274 | gnomAD-4.0.0 | 1.20036E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.31255E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/A | 0.7123 | likely_pathogenic | 0.7823 | pathogenic | -1.595 | Destabilizing | 0.854 | D | 0.597 | neutral | None | None | None | None | N |
| H/C | 0.2884 | likely_benign | 0.2934 | benign | -0.908 | Destabilizing | 0.996 | D | 0.718 | prob.delet. | None | None | None | None | N |
| H/D | 0.8113 | likely_pathogenic | 0.8771 | pathogenic | -1.49 | Destabilizing | 0.979 | D | 0.621 | neutral | N | 0.503394706 | None | None | N |
| H/E | 0.7765 | likely_pathogenic | 0.8367 | pathogenic | -1.334 | Destabilizing | 0.854 | D | 0.578 | neutral | None | None | None | None | N |
| H/F | 0.2451 | likely_benign | 0.2366 | benign | 0.171 | Stabilizing | 0.59 | D | 0.587 | neutral | None | None | None | None | N |
| H/G | 0.8719 | likely_pathogenic | 0.9117 | pathogenic | -1.968 | Destabilizing | 0.854 | D | 0.597 | neutral | None | None | None | None | N |
| H/I | 0.2977 | likely_benign | 0.3605 | ambiguous | -0.507 | Destabilizing | 0.953 | D | 0.68 | prob.neutral | None | None | None | None | N |
| H/K | 0.838 | likely_pathogenic | 0.8765 | pathogenic | -1.315 | Destabilizing | 0.953 | D | 0.612 | neutral | None | None | None | None | N |
| H/L | 0.157 | likely_benign | 0.1911 | benign | -0.507 | Destabilizing | 0.684 | D | 0.642 | neutral | N | 0.444943835 | None | None | N |
| H/M | 0.5538 | ambiguous | 0.6126 | pathogenic | -0.72 | Destabilizing | 0.996 | D | 0.658 | neutral | None | None | None | None | N |
| H/N | 0.2929 | likely_benign | 0.3528 | ambiguous | -1.617 | Destabilizing | 0.931 | D | 0.598 | neutral | N | 0.470724927 | None | None | N |
| H/P | 0.9294 | likely_pathogenic | 0.9542 | pathogenic | -0.858 | Destabilizing | 0.979 | D | 0.649 | neutral | N | 0.49768902 | None | None | N |
| H/Q | 0.4906 | ambiguous | 0.558 | ambiguous | -1.221 | Destabilizing | 0.979 | D | 0.593 | neutral | N | 0.492812353 | None | None | N |
| H/R | 0.531 | ambiguous | 0.5812 | pathogenic | -1.653 | Destabilizing | 0.939 | D | 0.591 | neutral | N | 0.457659629 | None | None | N |
| H/S | 0.5278 | ambiguous | 0.6133 | pathogenic | -1.718 | Destabilizing | 0.854 | D | 0.603 | neutral | None | None | None | None | N |
| H/T | 0.5549 | ambiguous | 0.6665 | pathogenic | -1.464 | Destabilizing | 0.953 | D | 0.627 | neutral | None | None | None | None | N |
| H/V | 0.3276 | likely_benign | 0.3985 | ambiguous | -0.858 | Destabilizing | 0.91 | D | 0.667 | neutral | None | None | None | None | N |
| H/W | 0.4352 | ambiguous | 0.4033 | ambiguous | 0.528 | Stabilizing | 0.02 | N | 0.533 | neutral | None | None | None | None | N |
| H/Y | 0.0949 | likely_benign | 0.0904 | benign | 0.422 | Stabilizing | 0.028 | N | 0.341 | neutral | N | 0.456046263 | 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.