Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29809 | 89650;89651;89652 | chr2:178553580;178553579;178553578 | chr2:179418307;179418306;179418305 |
| N2AB | 28168 | 84727;84728;84729 | chr2:178553580;178553579;178553578 | chr2:179418307;179418306;179418305 |
| N2A | 27241 | 81946;81947;81948 | chr2:178553580;178553579;178553578 | chr2:179418307;179418306;179418305 |
| N2B | 20744 | 62455;62456;62457 | chr2:178553580;178553579;178553578 | chr2:179418307;179418306;179418305 |
| Novex-1 | 20869 | 62830;62831;62832 | chr2:178553580;178553579;178553578 | chr2:179418307;179418306;179418305 |
| Novex-2 | 20936 | 63031;63032;63033 | chr2:178553580;178553579;178553578 | chr2:179418307;179418306;179418305 |
| 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/Q | rs72648238  |
-1.129 | 0.002 | N | 0.437 | 0.183 | None | gnomAD-2.1.1 | 6.42926E-04 | None | None | None | None | N | None | 1.65289E-04 | 9.04977E-04 | None | 3.87147E-04 | 0 | None | 0 | None | 4.39894E-04 | 9.6199E-04 | 8.43645E-04 |
| R/Q | rs72648238 |
-1.129 | 0.002 | N | 0.437 | 0.183 | None | gnomAD-3.1.2 | 8.01777E-04 | None | None | None | None | N | None | 3.13737E-04 | 9.81804E-04 | 0 | 8.64055E-04 | 0 | None | 1.88324E-04 | 0 | 1.29362E-03 | 0 | 4.78927E-04 |
| R/Q | rs72648238 |
-1.129 | 0.002 | N | 0.437 | 0.183 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| R/Q | rs72648238 |
-1.129 | 0.002 | N | 0.437 | 0.183 | None | gnomAD-4.0.0 | 7.98096E-04 | None | None | None | None | N | None | 2.13231E-04 | 8.33056E-04 | None | 5.06825E-04 | 0 | None | 4.21783E-04 | 1.15588E-03 | 9.51015E-04 | 0 | 8.16287E-04 |
| R/W | rs112777680 |
None | 0.984 | D | 0.711 | 0.531 | 0.544870321563 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/W | rs112777680 |
None | 0.984 | D | 0.711 | 0.531 | 0.544870321563 | gnomAD-4.0.0 | 1.30137E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 4.45673E-05 | None | 0 | 0 | 1.61044E-05 | 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 | 0.7975 | likely_pathogenic | 0.6965 | pathogenic | -1.758 | Destabilizing | 0.081 | N | 0.535 | neutral | None | None | None | None | N |
| R/C | 0.2824 | likely_benign | 0.2044 | benign | -1.731 | Destabilizing | 0.935 | D | 0.706 | prob.neutral | None | None | None | None | N |
| R/D | 0.983 | likely_pathogenic | 0.9642 | pathogenic | -0.864 | Destabilizing | 0.149 | N | 0.538 | neutral | None | None | None | None | N |
| R/E | 0.817 | likely_pathogenic | 0.7208 | pathogenic | -0.654 | Destabilizing | 0.035 | N | 0.571 | neutral | None | None | None | None | N |
| R/F | 0.9332 | likely_pathogenic | 0.8804 | pathogenic | -0.964 | Destabilizing | 0.791 | D | 0.661 | neutral | None | None | None | None | N |
| R/G | 0.8339 | likely_pathogenic | 0.7011 | pathogenic | -2.097 | Highly Destabilizing | 0.251 | N | 0.474 | neutral | D | 0.538348664 | None | None | N |
| R/H | 0.2519 | likely_benign | 0.1996 | benign | -1.988 | Destabilizing | 0.38 | N | 0.515 | neutral | None | None | None | None | N |
| R/I | 0.7113 | likely_pathogenic | 0.5605 | ambiguous | -0.781 | Destabilizing | 0.555 | D | 0.647 | neutral | None | None | None | None | N |
| R/K | 0.2302 | likely_benign | 0.1866 | benign | -1.281 | Destabilizing | None | N | 0.295 | neutral | None | None | None | None | N |
| R/L | 0.6737 | likely_pathogenic | 0.5441 | ambiguous | -0.781 | Destabilizing | 0.251 | N | 0.474 | neutral | N | 0.493012347 | None | None | N |
| R/M | 0.7302 | likely_pathogenic | 0.6088 | pathogenic | -1.335 | Destabilizing | 0.555 | D | 0.591 | neutral | None | None | None | None | N |
| R/N | 0.9107 | likely_pathogenic | 0.8508 | pathogenic | -1.235 | Destabilizing | 0.149 | N | 0.513 | neutral | None | None | None | None | N |
| R/P | 0.997 | likely_pathogenic | 0.993 | pathogenic | -1.095 | Destabilizing | 0.705 | D | 0.585 | neutral | D | 0.538855643 | None | None | N |
| R/Q | 0.1864 | likely_benign | 0.1465 | benign | -1.076 | Destabilizing | 0.002 | N | 0.437 | neutral | N | 0.480855893 | None | None | N |
| R/S | 0.8649 | likely_pathogenic | 0.7699 | pathogenic | -2.056 | Highly Destabilizing | 0.081 | N | 0.49 | neutral | None | None | None | None | N |
| R/T | 0.7359 | likely_pathogenic | 0.6082 | pathogenic | -1.644 | Destabilizing | 0.149 | N | 0.471 | neutral | None | None | None | None | N |
| R/V | 0.7571 | likely_pathogenic | 0.6233 | pathogenic | -1.095 | Destabilizing | 0.38 | N | 0.587 | neutral | None | None | None | None | N |
| R/W | 0.6451 | likely_pathogenic | 0.4984 | ambiguous | -0.538 | Destabilizing | 0.984 | D | 0.711 | prob.delet. | D | 0.527245848 | None | None | N |
| R/Y | 0.852 | likely_pathogenic | 0.7584 | pathogenic | -0.373 | Destabilizing | 0.555 | D | 0.619 | 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.