Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18265 | 55018;55019;55020 | chr2:178603894;178603893;178603892 | chr2:179468621;179468620;179468619 |
| N2AB | 16624 | 50095;50096;50097 | chr2:178603894;178603893;178603892 | chr2:179468621;179468620;179468619 |
| N2A | 15697 | 47314;47315;47316 | chr2:178603894;178603893;178603892 | chr2:179468621;179468620;179468619 |
| N2B | 9200 | 27823;27824;27825 | chr2:178603894;178603893;178603892 | chr2:179468621;179468620;179468619 |
| Novex-1 | 9325 | 28198;28199;28200 | chr2:178603894;178603893;178603892 | chr2:179468621;179468620;179468619 |
| Novex-2 | 9392 | 28399;28400;28401 | chr2:178603894;178603893;178603892 | chr2:179468621;179468620;179468619 |
| 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 | rs2054138018  |
None | 0.002 | N | 0.173 | 0.066 | 0.368743488249 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/A | rs2054138018 |
None | 0.002 | N | 0.173 | 0.066 | 0.368743488249 | gnomAD-4.0.0 | 3.91767E-06 | None | None | None | None | N | None | 1.70126E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 4.91328E-06 | 0 | 0 |
| V/I | rs397517621 |
None | None | N | 0.087 | 0.048 | 0.104622674875 | gnomAD-4.0.0 | 1.61921E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.92423E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1486 | likely_benign | 0.1041 | benign | -1.114 | Destabilizing | 0.002 | N | 0.173 | neutral | N | 0.454235322 | None | None | N |
| V/C | 0.5892 | likely_pathogenic | 0.5115 | ambiguous | -0.787 | Destabilizing | 0.439 | N | 0.319 | neutral | None | None | None | None | N |
| V/D | 0.2457 | likely_benign | 0.1762 | benign | -0.771 | Destabilizing | 0.013 | N | 0.606 | neutral | N | 0.466592164 | None | None | N |
| V/E | 0.1842 | likely_benign | 0.124 | benign | -0.837 | Destabilizing | None | N | 0.417 | neutral | None | None | None | None | N |
| V/F | 0.1335 | likely_benign | 0.0978 | benign | -1.03 | Destabilizing | None | N | 0.168 | neutral | N | 0.451176374 | None | None | N |
| V/G | 0.2319 | likely_benign | 0.1648 | benign | -1.35 | Destabilizing | 0.026 | N | 0.493 | neutral | N | 0.466592164 | None | None | N |
| V/H | 0.4429 | ambiguous | 0.3111 | benign | -0.815 | Destabilizing | 0.204 | N | 0.484 | neutral | None | None | None | None | N |
| V/I | 0.0686 | likely_benign | 0.064 | benign | -0.602 | Destabilizing | None | N | 0.087 | neutral | N | 0.405057296 | None | None | N |
| V/K | 0.2218 | likely_benign | 0.1608 | benign | -0.869 | Destabilizing | 0.007 | N | 0.417 | neutral | None | None | None | None | N |
| V/L | 0.1337 | likely_benign | 0.1016 | benign | -0.602 | Destabilizing | None | N | 0.05 | neutral | N | 0.415754292 | None | None | N |
| V/M | 0.1135 | likely_benign | 0.0897 | benign | -0.439 | Destabilizing | 0.06 | N | 0.311 | neutral | None | None | None | None | N |
| V/N | 0.2139 | likely_benign | 0.147 | benign | -0.579 | Destabilizing | 0.035 | N | 0.655 | prob.neutral | None | None | None | None | N |
| V/P | 0.3232 | likely_benign | 0.2481 | benign | -0.737 | Destabilizing | 0.068 | N | 0.639 | neutral | None | None | None | None | N |
| V/Q | 0.2557 | likely_benign | 0.1807 | benign | -0.831 | Destabilizing | 0.018 | N | 0.616 | neutral | None | None | None | None | N |
| V/R | 0.2233 | likely_benign | 0.1615 | benign | -0.281 | Destabilizing | None | N | 0.421 | neutral | None | None | None | None | N |
| V/S | 0.1904 | likely_benign | 0.1299 | benign | -1.06 | Destabilizing | 0.007 | N | 0.365 | neutral | None | None | None | None | N |
| V/T | 0.127 | likely_benign | 0.0918 | benign | -1.022 | Destabilizing | None | N | 0.105 | neutral | None | None | None | None | N |
| V/W | 0.5899 | likely_pathogenic | 0.4499 | ambiguous | -1.115 | Destabilizing | 0.747 | D | 0.494 | neutral | None | None | None | None | N |
| V/Y | 0.3582 | ambiguous | 0.2659 | benign | -0.839 | Destabilizing | 0.018 | N | 0.524 | 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.