Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 6256 | 18991;18992;18993 | chr2:178729390;178729389;178729388 | chr2:179594117;179594116;179594115 |
| N2AB | 5939 | 18040;18041;18042 | chr2:178729390;178729389;178729388 | chr2:179594117;179594116;179594115 |
| N2A | 5012 | 15259;15260;15261 | chr2:178729390;178729389;178729388 | chr2:179594117;179594116;179594115 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs747713653  |
None | 1.0 | D | 0.825 | 0.586 | 0.756636443533 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/F | rs747713653 |
None | 1.0 | D | 0.825 | 0.586 | 0.756636443533 | gnomAD-4.0.0 | 1.85934E-06 | None | None | None | None | N | None | 0 | 3.33578E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.60133E-05 |
| L/I | rs747713653 |
-0.515 | 0.999 | N | 0.667 | 0.537 | 0.711290743721 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.94E-06 | 0 |
| L/I | rs747713653 |
-0.515 | 0.999 | N | 0.667 | 0.537 | 0.711290743721 | gnomAD-4.0.0 | 6.84281E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99552E-07 | 0 | 0 |
| L/R | rs780526976 |
-1.943 | 1.0 | D | 0.913 | 0.826 | 0.872484263163 | gnomAD-2.1.1 | 3.58E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 3.19744E-04 | 7.85E-06 | 1.40568E-04 |
| L/R | rs780526976 |
-1.943 | 1.0 | D | 0.913 | 0.826 | 0.872484263163 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 2.83286E-04 | 0 | 0 | 0 | 0 |
| L/R | rs780526976 |
-1.943 | 1.0 | D | 0.913 | 0.826 | 0.872484263163 | gnomAD-4.0.0 | 4.74189E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 4.08112E-04 | 0 | 2.15446E-05 | 0 | 5.69022E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9056 | likely_pathogenic | 0.9091 | pathogenic | -2.51 | Highly Destabilizing | 0.999 | D | 0.765 | deleterious | None | None | None | None | N |
| L/C | 0.8355 | likely_pathogenic | 0.8368 | pathogenic | -1.871 | Destabilizing | 1.0 | D | 0.86 | deleterious | None | None | None | None | N |
| L/D | 0.9992 | likely_pathogenic | 0.999 | pathogenic | -3.353 | Highly Destabilizing | 1.0 | D | 0.921 | deleterious | None | None | None | None | N |
| L/E | 0.9947 | likely_pathogenic | 0.9938 | pathogenic | -3.024 | Highly Destabilizing | 1.0 | D | 0.903 | deleterious | None | None | None | None | N |
| L/F | 0.4943 | ambiguous | 0.4698 | ambiguous | -1.566 | Destabilizing | 1.0 | D | 0.825 | deleterious | D | 0.539638198 | None | None | N |
| L/G | 0.9791 | likely_pathogenic | 0.9772 | pathogenic | -3.117 | Highly Destabilizing | 1.0 | D | 0.89 | deleterious | None | None | None | None | N |
| L/H | 0.9776 | likely_pathogenic | 0.972 | pathogenic | -3.011 | Highly Destabilizing | 1.0 | D | 0.892 | deleterious | D | 0.557795359 | None | None | N |
| L/I | 0.1833 | likely_benign | 0.1981 | benign | -0.675 | Destabilizing | 0.999 | D | 0.667 | neutral | N | 0.522001242 | None | None | N |
| L/K | 0.9903 | likely_pathogenic | 0.9887 | pathogenic | -1.964 | Destabilizing | 1.0 | D | 0.899 | deleterious | None | None | None | None | N |
| L/M | 0.1997 | likely_benign | 0.2301 | benign | -0.946 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| L/N | 0.9931 | likely_pathogenic | 0.9926 | pathogenic | -2.73 | Highly Destabilizing | 1.0 | D | 0.923 | deleterious | None | None | None | None | N |
| L/P | 0.9972 | likely_pathogenic | 0.9964 | pathogenic | -1.279 | Destabilizing | 1.0 | D | 0.922 | deleterious | D | 0.557795359 | None | None | N |
| L/Q | 0.9677 | likely_pathogenic | 0.964 | pathogenic | -2.326 | Highly Destabilizing | 1.0 | D | 0.925 | deleterious | None | None | None | None | N |
| L/R | 0.9772 | likely_pathogenic | 0.9711 | pathogenic | -2.178 | Highly Destabilizing | 1.0 | D | 0.913 | deleterious | D | 0.575899614 | None | None | N |
| L/S | 0.9833 | likely_pathogenic | 0.9827 | pathogenic | -3.231 | Highly Destabilizing | 1.0 | D | 0.897 | deleterious | None | None | None | None | N |
| L/T | 0.9465 | likely_pathogenic | 0.9469 | pathogenic | -2.728 | Highly Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | N |
| L/V | 0.2374 | likely_benign | 0.2517 | benign | -1.279 | Destabilizing | 0.999 | D | 0.68 | prob.neutral | D | 0.530674975 | None | None | N |
| L/W | 0.9471 | likely_pathogenic | 0.9246 | pathogenic | -1.983 | Destabilizing | 1.0 | D | 0.882 | deleterious | None | None | None | None | N |
| L/Y | 0.9303 | likely_pathogenic | 0.9184 | pathogenic | -1.755 | Destabilizing | 1.0 | D | 0.863 | deleterious | 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.