Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26336 | 79231;79232;79233 | chr2:178567126;178567125;178567124 | chr2:179431853;179431852;179431851 |
| N2AB | 24695 | 74308;74309;74310 | chr2:178567126;178567125;178567124 | chr2:179431853;179431852;179431851 |
| N2A | 23768 | 71527;71528;71529 | chr2:178567126;178567125;178567124 | chr2:179431853;179431852;179431851 |
| N2B | 17271 | 52036;52037;52038 | chr2:178567126;178567125;178567124 | chr2:179431853;179431852;179431851 |
| Novex-1 | 17396 | 52411;52412;52413 | chr2:178567126;178567125;178567124 | chr2:179431853;179431852;179431851 |
| Novex-2 | 17463 | 52612;52613;52614 | chr2:178567126;178567125;178567124 | chr2:179431853;179431852;179431851 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs1706198787  |
None | 0.489 | N | 0.499 | 0.251 | 0.603275841759 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/A | rs1706198787 |
None | 0.489 | N | 0.499 | 0.251 | 0.603275841759 | gnomAD-4.0.0 | 6.57583E-06 | None | None | None | None | I | None | 2.41418E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs1706199858 |
None | 0.489 | N | 0.485 | 0.073 | 0.442672919754 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs1706199858 |
None | 0.489 | N | 0.485 | 0.073 | 0.442672919754 | gnomAD-4.0.0 | 4.06011E-06 | None | None | None | None | I | None | 1.7477E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.40995E-06 | 4.69704E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1889 | likely_benign | 0.1825 | benign | -0.971 | Destabilizing | 0.489 | N | 0.499 | neutral | N | 0.49877832 | None | None | I |
| V/C | 0.7541 | likely_pathogenic | 0.763 | pathogenic | -0.764 | Destabilizing | 0.998 | D | 0.729 | prob.delet. | None | None | None | None | I |
| V/D | 0.5706 | likely_pathogenic | 0.6415 | pathogenic | -0.736 | Destabilizing | 0.942 | D | 0.755 | deleterious | N | 0.516364003 | None | None | I |
| V/E | 0.3786 | ambiguous | 0.4376 | ambiguous | -0.819 | Destabilizing | 0.956 | D | 0.731 | prob.delet. | None | None | None | None | I |
| V/F | 0.2725 | likely_benign | 0.3137 | benign | -0.941 | Destabilizing | 0.942 | D | 0.724 | prob.delet. | N | 0.475016089 | None | None | I |
| V/G | 0.3006 | likely_benign | 0.3073 | benign | -1.178 | Destabilizing | 0.942 | D | 0.694 | prob.neutral | N | 0.520116385 | None | None | I |
| V/H | 0.6362 | likely_pathogenic | 0.6818 | pathogenic | -0.65 | Destabilizing | 0.998 | D | 0.755 | deleterious | None | None | None | None | I |
| V/I | 0.0763 | likely_benign | 0.0783 | benign | -0.551 | Destabilizing | 0.489 | N | 0.485 | neutral | N | 0.462108231 | None | None | I |
| V/K | 0.4336 | ambiguous | 0.5023 | ambiguous | -0.859 | Destabilizing | 0.956 | D | 0.698 | prob.neutral | None | None | None | None | I |
| V/L | 0.1457 | likely_benign | 0.149 | benign | -0.551 | Destabilizing | 0.006 | N | 0.207 | neutral | N | 0.472074508 | None | None | I |
| V/M | 0.1108 | likely_benign | 0.1181 | benign | -0.444 | Destabilizing | 0.956 | D | 0.627 | neutral | None | None | None | None | I |
| V/N | 0.3101 | likely_benign | 0.3332 | benign | -0.588 | Destabilizing | 0.956 | D | 0.76 | deleterious | None | None | None | None | I |
| V/P | 0.5748 | likely_pathogenic | 0.525 | ambiguous | -0.655 | Destabilizing | 0.978 | D | 0.751 | deleterious | None | None | None | None | I |
| V/Q | 0.3293 | likely_benign | 0.3635 | ambiguous | -0.846 | Destabilizing | 0.978 | D | 0.759 | deleterious | None | None | None | None | I |
| V/R | 0.4139 | ambiguous | 0.4745 | ambiguous | -0.249 | Destabilizing | 0.956 | D | 0.761 | deleterious | None | None | None | None | I |
| V/S | 0.2602 | likely_benign | 0.2622 | benign | -1.01 | Destabilizing | 0.915 | D | 0.645 | neutral | None | None | None | None | I |
| V/T | 0.1802 | likely_benign | 0.1831 | benign | -0.993 | Destabilizing | 0.019 | N | 0.331 | neutral | None | None | None | None | I |
| V/W | 0.8661 | likely_pathogenic | 0.8877 | pathogenic | -1.023 | Destabilizing | 0.998 | D | 0.729 | prob.delet. | None | None | None | None | I |
| V/Y | 0.6784 | likely_pathogenic | 0.72 | pathogenic | -0.753 | Destabilizing | 0.993 | D | 0.729 | prob.delet. | 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.