Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15492 | 46699;46700;46701 | chr2:178619843;178619842;178619841 | chr2:179484570;179484569;179484568 |
| N2AB | 13851 | 41776;41777;41778 | chr2:178619843;178619842;178619841 | chr2:179484570;179484569;179484568 |
| N2A | 12924 | 38995;38996;38997 | chr2:178619843;178619842;178619841 | chr2:179484570;179484569;179484568 |
| N2B | 6427 | 19504;19505;19506 | chr2:178619843;178619842;178619841 | chr2:179484570;179484569;179484568 |
| Novex-1 | 6552 | 19879;19880;19881 | chr2:178619843;178619842;178619841 | chr2:179484570;179484569;179484568 |
| Novex-2 | 6619 | 20080;20081;20082 | chr2:178619843;178619842;178619841 | chr2:179484570;179484569;179484568 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/D | None | None | 0.994 | N | 0.593 | 0.413 | 0.747887111329 | gnomAD-4.0.0 | 1.59536E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86472E-06 | 0 | 0 |
| A/T | rs1370664332  |
-0.714 | 0.98 | N | 0.49 | 0.262 | 0.350307294319 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.96E-06 | 0 |
| A/T | rs1370664332 |
-0.714 | 0.98 | N | 0.49 | 0.262 | 0.350307294319 | gnomAD-4.0.0 | 3.19057E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.72951E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.6838 | likely_pathogenic | 0.6792 | pathogenic | -0.788 | Destabilizing | 1.0 | D | 0.525 | neutral | None | None | None | None | N |
| A/D | 0.4061 | ambiguous | 0.3386 | benign | -0.573 | Destabilizing | 0.994 | D | 0.593 | neutral | N | 0.498993076 | None | None | N |
| A/E | 0.2865 | likely_benign | 0.2367 | benign | -0.686 | Destabilizing | 0.985 | D | 0.485 | neutral | None | None | None | None | N |
| A/F | 0.4377 | ambiguous | 0.3831 | ambiguous | -0.877 | Destabilizing | 0.999 | D | 0.641 | neutral | None | None | None | None | N |
| A/G | 0.1891 | likely_benign | 0.1804 | benign | -0.616 | Destabilizing | 0.98 | D | 0.489 | neutral | N | 0.499531806 | None | None | N |
| A/H | 0.5543 | ambiguous | 0.5207 | ambiguous | -0.688 | Destabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | N |
| A/I | 0.2939 | likely_benign | 0.2639 | benign | -0.3 | Destabilizing | 0.999 | D | 0.513 | neutral | None | None | None | None | N |
| A/K | 0.4356 | ambiguous | 0.385 | ambiguous | -0.885 | Destabilizing | 0.985 | D | 0.483 | neutral | None | None | None | None | N |
| A/L | 0.1919 | likely_benign | 0.1759 | benign | -0.3 | Destabilizing | 0.985 | D | 0.503 | neutral | None | None | None | None | N |
| A/M | 0.2493 | likely_benign | 0.2337 | benign | -0.346 | Destabilizing | 1.0 | D | 0.534 | neutral | None | None | None | None | N |
| A/N | 0.3003 | likely_benign | 0.2719 | benign | -0.552 | Destabilizing | 0.999 | D | 0.631 | neutral | None | None | None | None | N |
| A/P | 0.1449 | likely_benign | 0.1459 | benign | -0.322 | Destabilizing | 0.011 | N | 0.337 | neutral | N | 0.4247239 | None | None | N |
| A/Q | 0.324 | likely_benign | 0.3003 | benign | -0.784 | Destabilizing | 0.999 | D | 0.505 | neutral | None | None | None | None | N |
| A/R | 0.4601 | ambiguous | 0.3965 | ambiguous | -0.451 | Destabilizing | 0.999 | D | 0.506 | neutral | None | None | None | None | N |
| A/S | 0.1106 | likely_benign | 0.105 | benign | -0.813 | Destabilizing | 0.98 | D | 0.531 | neutral | N | 0.45228015 | None | None | N |
| A/T | 0.127 | likely_benign | 0.1131 | benign | -0.837 | Destabilizing | 0.98 | D | 0.49 | neutral | N | 0.404632296 | None | None | N |
| A/V | 0.1571 | likely_benign | 0.1399 | benign | -0.322 | Destabilizing | 0.98 | D | 0.484 | neutral | N | 0.389053652 | None | None | N |
| A/W | 0.863 | likely_pathogenic | 0.8333 | pathogenic | -1.09 | Destabilizing | 1.0 | D | 0.702 | prob.neutral | None | None | None | None | N |
| A/Y | 0.5674 | likely_pathogenic | 0.537 | ambiguous | -0.718 | Destabilizing | 0.999 | D | 0.641 | 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.