Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29527 | 88804;88805;88806 | chr2:178554880;178554879;178554878 | chr2:179419607;179419606;179419605 |
| N2AB | 27886 | 83881;83882;83883 | chr2:178554880;178554879;178554878 | chr2:179419607;179419606;179419605 |
| N2A | 26959 | 81100;81101;81102 | chr2:178554880;178554879;178554878 | chr2:179419607;179419606;179419605 |
| N2B | 20462 | 61609;61610;61611 | chr2:178554880;178554879;178554878 | chr2:179419607;179419606;179419605 |
| Novex-1 | 20587 | 61984;61985;61986 | chr2:178554880;178554879;178554878 | chr2:179419607;179419606;179419605 |
| Novex-2 | 20654 | 62185;62186;62187 | chr2:178554880;178554879;178554878 | chr2:179419607;179419606;179419605 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | rs779247881  |
-0.812 | 0.722 | N | 0.672 | 0.326 | 0.677622474905 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| R/G | rs779247881 |
-0.812 | 0.722 | N | 0.672 | 0.326 | 0.677622474905 | gnomAD-4.0.0 | 6.84186E-06 | None | None | None | None | N | None | 2.98704E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79886E-06 | 6.95604E-05 | 1.65656E-05 |
| R/T | rs1450823990 |
-0.322 | 0.722 | N | 0.685 | 0.302 | 0.548188646194 | gnomAD-2.1.1 | 6.37E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.29668E-04 | 0 |
| R/T | rs1450823990 |
-0.322 | 0.722 | N | 0.685 | 0.302 | 0.548188646194 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| R/T | rs1450823990 |
-0.322 | 0.722 | N | 0.685 | 0.302 | 0.548188646194 | gnomAD-4.0.0 | 5.12392E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.57089E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.2941 | likely_benign | 0.2807 | benign | -0.583 | Destabilizing | 0.633 | D | 0.653 | neutral | None | None | None | None | N |
| R/C | 0.154 | likely_benign | 0.1536 | benign | -0.515 | Destabilizing | 0.996 | D | 0.725 | prob.delet. | None | None | None | None | N |
| R/D | 0.5288 | ambiguous | 0.5132 | ambiguous | 0.043 | Stabilizing | 0.923 | D | 0.674 | neutral | None | None | None | None | N |
| R/E | 0.3048 | likely_benign | 0.2996 | benign | 0.149 | Stabilizing | 0.633 | D | 0.6 | neutral | None | None | None | None | N |
| R/F | 0.4851 | ambiguous | 0.4608 | ambiguous | -0.531 | Destabilizing | 0.987 | D | 0.725 | prob.delet. | None | None | None | None | N |
| R/G | 0.2187 | likely_benign | 0.2115 | benign | -0.87 | Destabilizing | 0.722 | D | 0.672 | neutral | N | 0.483534801 | None | None | N |
| R/H | 0.0842 | likely_benign | 0.0848 | benign | -1.209 | Destabilizing | 0.961 | D | 0.623 | neutral | None | None | None | None | N |
| R/I | 0.2351 | likely_benign | 0.2207 | benign | 0.172 | Stabilizing | 0.949 | D | 0.729 | prob.delet. | N | 0.46485304 | None | None | N |
| R/K | 0.0922 | likely_benign | 0.0906 | benign | -0.577 | Destabilizing | 0.003 | N | 0.23 | neutral | N | 0.375404471 | None | None | N |
| R/L | 0.2029 | likely_benign | 0.1952 | benign | 0.172 | Stabilizing | 0.775 | D | 0.672 | neutral | None | None | None | None | N |
| R/M | 0.2151 | likely_benign | 0.2087 | benign | -0.137 | Destabilizing | 0.996 | D | 0.691 | prob.neutral | None | None | None | None | N |
| R/N | 0.3901 | ambiguous | 0.3757 | ambiguous | -0.041 | Destabilizing | 0.923 | D | 0.629 | neutral | None | None | None | None | N |
| R/P | 0.5711 | likely_pathogenic | 0.5426 | ambiguous | -0.058 | Destabilizing | 0.961 | D | 0.733 | prob.delet. | None | None | None | None | N |
| R/Q | 0.0941 | likely_benign | 0.0955 | benign | -0.231 | Destabilizing | 0.858 | D | 0.653 | neutral | None | None | None | None | N |
| R/S | 0.3362 | likely_benign | 0.3271 | benign | -0.753 | Destabilizing | 0.565 | D | 0.689 | prob.neutral | N | 0.41888589 | None | None | N |
| R/T | 0.1399 | likely_benign | 0.1363 | benign | -0.475 | Destabilizing | 0.722 | D | 0.685 | prob.neutral | N | 0.388968414 | None | None | N |
| R/V | 0.3008 | likely_benign | 0.2873 | benign | -0.058 | Destabilizing | 0.923 | D | 0.704 | prob.neutral | None | None | None | None | N |
| R/W | 0.158 | likely_benign | 0.1604 | benign | -0.262 | Destabilizing | 0.996 | D | 0.677 | prob.neutral | None | None | None | None | N |
| R/Y | 0.333 | likely_benign | 0.3209 | benign | 0.061 | Stabilizing | 0.987 | D | 0.736 | prob.delet. | 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.