Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27158 | 81697;81698;81699 | chr2:178564660;178564659;178564658 | chr2:179429387;179429386;179429385 |
| N2AB | 25517 | 76774;76775;76776 | chr2:178564660;178564659;178564658 | chr2:179429387;179429386;179429385 |
| N2A | 24590 | 73993;73994;73995 | chr2:178564660;178564659;178564658 | chr2:179429387;179429386;179429385 |
| N2B | 18093 | 54502;54503;54504 | chr2:178564660;178564659;178564658 | chr2:179429387;179429386;179429385 |
| Novex-1 | 18218 | 54877;54878;54879 | chr2:178564660;178564659;178564658 | chr2:179429387;179429386;179429385 |
| Novex-2 | 18285 | 55078;55079;55080 | chr2:178564660;178564659;178564658 | chr2:179429387;179429386;179429385 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | rs200771189  |
-1.142 | None | N | 0.249 | 0.098 | None | gnomAD-2.1.1 | 4.11328E-04 | None | None | None | None | I | None | 8.27E-05 | 1.98413E-04 | None | 0 | 0 | None | 0 | None | 4.80154E-04 | 6.96859E-04 | 7.03631E-04 |
| P/A | rs200771189 |
-1.142 | None | N | 0.249 | 0.098 | None | gnomAD-3.1.2 | 5.7206E-04 | None | None | None | None | I | None | 2.17213E-04 | 1.44262E-03 | 0 | 0 | 0 | None | 1.88679E-04 | 0 | 7.94048E-04 | 0 | 0 |
| P/A | rs200771189 |
-1.142 | None | N | 0.249 | 0.098 | None | gnomAD-4.0.0 | 5.18792E-04 | None | None | None | None | I | None | 1.73602E-04 | 5.00501E-04 | None | 0 | 0 | None | 5.31499E-04 | 0 | 6.30666E-04 | 0 | 2.56246E-04 |
| P/R | rs762635284 |
-0.245 | 0.055 | N | 0.603 | 0.305 | 0.351830644314 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.61E-05 | None | 0 | None | 0 | 0 | 0 |
| P/R | rs762635284 |
-0.245 | 0.055 | N | 0.603 | 0.305 | 0.351830644314 | gnomAD-4.0.0 | 1.59196E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.78133E-05 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0574 | likely_benign | 0.0547 | benign | -1.109 | Destabilizing | None | N | 0.249 | neutral | N | 0.479787128 | None | None | I |
| P/C | 0.2872 | likely_benign | 0.2561 | benign | -0.856 | Destabilizing | None | N | 0.482 | neutral | None | None | None | None | I |
| P/D | 0.5993 | likely_pathogenic | 0.5229 | ambiguous | -0.653 | Destabilizing | 0.072 | N | 0.463 | neutral | None | None | None | None | I |
| P/E | 0.3855 | ambiguous | 0.34 | benign | -0.731 | Destabilizing | 0.031 | N | 0.411 | neutral | None | None | None | None | I |
| P/F | 0.355 | ambiguous | 0.3265 | benign | -1.075 | Destabilizing | 0.214 | N | 0.627 | neutral | None | None | None | None | I |
| P/G | 0.2878 | likely_benign | 0.2489 | benign | -1.321 | Destabilizing | 0.016 | N | 0.45 | neutral | None | None | None | None | I |
| P/H | 0.2264 | likely_benign | 0.1918 | benign | -0.771 | Destabilizing | 0.56 | D | 0.583 | neutral | N | 0.511020335 | None | None | I |
| P/I | 0.1973 | likely_benign | 0.1941 | benign | -0.671 | Destabilizing | 0.016 | N | 0.429 | neutral | None | None | None | None | I |
| P/K | 0.4062 | ambiguous | 0.3651 | ambiguous | -0.812 | Destabilizing | 0.031 | N | 0.411 | neutral | None | None | None | None | I |
| P/L | 0.1134 | likely_benign | 0.1055 | benign | -0.671 | Destabilizing | 0.005 | N | 0.439 | neutral | N | 0.497129134 | None | None | I |
| P/M | 0.2233 | likely_benign | 0.213 | benign | -0.513 | Destabilizing | 0.356 | N | 0.583 | neutral | None | None | None | None | I |
| P/N | 0.3105 | likely_benign | 0.2653 | benign | -0.521 | Destabilizing | 0.072 | N | 0.585 | neutral | None | None | None | None | I |
| P/Q | 0.1879 | likely_benign | 0.1634 | benign | -0.791 | Destabilizing | 0.136 | N | 0.575 | neutral | None | None | None | None | I |
| P/R | 0.2908 | likely_benign | 0.2546 | benign | -0.236 | Destabilizing | 0.055 | N | 0.603 | neutral | N | 0.510006377 | None | None | I |
| P/S | 0.1142 | likely_benign | 0.1004 | benign | -1.012 | Destabilizing | 0.001 | N | 0.263 | neutral | N | 0.468682532 | None | None | I |
| P/T | 0.0918 | likely_benign | 0.0857 | benign | -0.987 | Destabilizing | 0.012 | N | 0.425 | neutral | N | 0.489686849 | None | None | I |
| P/V | 0.1275 | likely_benign | 0.1273 | benign | -0.781 | Destabilizing | None | N | 0.363 | neutral | None | None | None | None | I |
| P/W | 0.6098 | likely_pathogenic | 0.563 | ambiguous | -1.114 | Destabilizing | 0.864 | D | 0.619 | neutral | None | None | None | None | I |
| P/Y | 0.3725 | ambiguous | 0.3328 | benign | -0.847 | Destabilizing | 0.356 | N | 0.629 | neutral | 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.