Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21867 | 65824;65825;65826 | chr2:178583204;178583203;178583202 | chr2:179447931;179447930;179447929 |
| N2AB | 20226 | 60901;60902;60903 | chr2:178583204;178583203;178583202 | chr2:179447931;179447930;179447929 |
| N2A | 19299 | 58120;58121;58122 | chr2:178583204;178583203;178583202 | chr2:179447931;179447930;179447929 |
| N2B | 12802 | 38629;38630;38631 | chr2:178583204;178583203;178583202 | chr2:179447931;179447930;179447929 |
| Novex-1 | 12927 | 39004;39005;39006 | chr2:178583204;178583203;178583202 | chr2:179447931;179447930;179447929 |
| Novex-2 | 12994 | 39205;39206;39207 | chr2:178583204;178583203;178583202 | chr2:179447931;179447930;179447929 |
| 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 | None | None | 0.165 | N | 0.589 | 0.238 | 0.520694202979 | gnomAD-4.0.0 | 3.21161E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.90141E-05 | 0 |
| V/M | rs769884849  |
-0.575 | 0.457 | N | 0.677 | 0.095 | 0.323615622048 | gnomAD-2.1.1 | 3.29E-05 | None | None | None | None | N | None | 0 | 5.85E-05 | None | 0 | 2.82965E-04 | None | 0 | None | 0 | 9.14E-06 | 0 |
| V/M | rs769884849 |
-0.575 | 0.457 | N | 0.677 | 0.095 | 0.323615622048 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.94024E-04 | None | 0 | 0 | 0 | 0 | 0 |
| V/M | rs769884849 |
-0.575 | 0.457 | N | 0.677 | 0.095 | 0.323615622048 | gnomAD-4.0.0 | 7.46802E-06 | None | None | None | None | N | None | 0 | 3.3493E-05 | None | 0 | 2.02038E-04 | None | 0 | 0 | 8.50596E-07 | 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 | 0.1458 | likely_benign | 0.1233 | benign | -0.342 | Destabilizing | 0.165 | N | 0.589 | neutral | N | 0.521604826 | None | None | N |
| V/C | 0.7936 | likely_pathogenic | 0.7307 | pathogenic | -0.861 | Destabilizing | 0.981 | D | 0.649 | neutral | None | None | None | None | N |
| V/D | 0.3653 | ambiguous | 0.2967 | benign | -0.242 | Destabilizing | 0.932 | D | 0.707 | prob.neutral | None | None | None | None | N |
| V/E | 0.31 | likely_benign | 0.2642 | benign | -0.354 | Destabilizing | 0.773 | D | 0.685 | prob.neutral | N | 0.487838241 | None | None | N |
| V/F | 0.2087 | likely_benign | 0.1828 | benign | -0.687 | Destabilizing | 0.527 | D | 0.687 | prob.neutral | None | None | None | None | N |
| V/G | 0.2322 | likely_benign | 0.1943 | benign | -0.399 | Destabilizing | 0.773 | D | 0.693 | prob.neutral | N | 0.490626626 | None | None | N |
| V/H | 0.6056 | likely_pathogenic | 0.5224 | ambiguous | 0.006 | Stabilizing | 0.981 | D | 0.684 | prob.neutral | None | None | None | None | N |
| V/I | 0.0827 | likely_benign | 0.0792 | benign | -0.333 | Destabilizing | 0.001 | N | 0.249 | neutral | None | None | None | None | N |
| V/K | 0.4204 | ambiguous | 0.3663 | ambiguous | -0.38 | Destabilizing | 0.818 | D | 0.674 | neutral | None | None | None | None | N |
| V/L | 0.1598 | likely_benign | 0.1396 | benign | -0.333 | Destabilizing | None | N | 0.26 | neutral | N | 0.503885856 | None | None | N |
| V/M | 0.1401 | likely_benign | 0.129 | benign | -0.577 | Destabilizing | 0.457 | N | 0.677 | prob.neutral | N | 0.479105737 | None | None | N |
| V/N | 0.3133 | likely_benign | 0.2585 | benign | -0.222 | Destabilizing | 0.932 | D | 0.701 | prob.neutral | None | None | None | None | N |
| V/P | 0.2436 | likely_benign | 0.2036 | benign | -0.308 | Destabilizing | 0.932 | D | 0.686 | prob.neutral | None | None | None | None | N |
| V/Q | 0.365 | ambiguous | 0.3137 | benign | -0.414 | Destabilizing | 0.932 | D | 0.679 | prob.neutral | None | None | None | None | N |
| V/R | 0.4143 | ambiguous | 0.35 | ambiguous | 0.047 | Stabilizing | 0.818 | D | 0.712 | prob.delet. | None | None | None | None | N |
| V/S | 0.2291 | likely_benign | 0.1892 | benign | -0.552 | Destabilizing | 0.818 | D | 0.681 | prob.neutral | None | None | None | None | N |
| V/T | 0.1847 | likely_benign | 0.1593 | benign | -0.571 | Destabilizing | 0.388 | N | 0.6 | neutral | None | None | None | None | N |
| V/W | 0.8297 | likely_pathogenic | 0.7693 | pathogenic | -0.741 | Destabilizing | 0.981 | D | 0.704 | prob.neutral | None | None | None | None | N |
| V/Y | 0.5917 | likely_pathogenic | 0.5144 | ambiguous | -0.474 | Destabilizing | 0.818 | D | 0.698 | prob.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.