Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20318 | 61177;61178;61179 | chr2:178590773;178590772;178590771 | chr2:179455500;179455499;179455498 |
| N2AB | 18677 | 56254;56255;56256 | chr2:178590773;178590772;178590771 | chr2:179455500;179455499;179455498 |
| N2A | 17750 | 53473;53474;53475 | chr2:178590773;178590772;178590771 | chr2:179455500;179455499;179455498 |
| N2B | 11253 | 33982;33983;33984 | chr2:178590773;178590772;178590771 | chr2:179455500;179455499;179455498 |
| Novex-1 | 11378 | 34357;34358;34359 | chr2:178590773;178590772;178590771 | chr2:179455500;179455499;179455498 |
| Novex-2 | 11445 | 34558;34559;34560 | chr2:178590773;178590772;178590771 | chr2:179455500;179455499;179455498 |
| 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 | rs1559584844  |
None | 0.78 | N | 0.499 | 0.241 | 0.498065138572 | gnomAD-4.0.0 | 9.60257E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.05E-05 | 0 | 0 |
| V/L | rs373150402 |
-0.147 | 0.437 | N | 0.341 | 0.191 | 0.31077124679 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.6E-05 | None | 0 | None | 0 | 0 | 0 |
| V/M | rs373150402 |
-0.26 | 0.968 | N | 0.545 | 0.241 | None | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| V/M | rs373150402 |
-0.26 | 0.968 | N | 0.545 | 0.241 | None | gnomAD-4.0.0 | 1.37455E-06 | None | None | None | None | N | None | 3.0003E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 9.03429E-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 | 0.3673 | ambiguous | 0.4287 | ambiguous | -0.998 | Destabilizing | 0.78 | D | 0.499 | neutral | N | 0.474263878 | None | None | N |
| V/C | 0.7258 | likely_pathogenic | 0.7457 | pathogenic | -0.774 | Destabilizing | 0.999 | D | 0.604 | neutral | None | None | None | None | N |
| V/D | 0.7175 | likely_pathogenic | 0.7802 | pathogenic | -0.696 | Destabilizing | 0.996 | D | 0.684 | prob.neutral | None | None | None | None | N |
| V/E | 0.5369 | ambiguous | 0.5865 | pathogenic | -0.729 | Destabilizing | 0.995 | D | 0.642 | neutral | N | 0.473205085 | None | None | N |
| V/F | 0.2491 | likely_benign | 0.2866 | benign | -0.753 | Destabilizing | 0.976 | D | 0.593 | neutral | None | None | None | None | N |
| V/G | 0.372 | ambiguous | 0.4156 | ambiguous | -1.25 | Destabilizing | 0.995 | D | 0.685 | prob.neutral | N | 0.464857417 | None | None | N |
| V/H | 0.6943 | likely_pathogenic | 0.7451 | pathogenic | -0.676 | Destabilizing | 0.999 | D | 0.7 | prob.neutral | None | None | None | None | N |
| V/I | 0.0794 | likely_benign | 0.0853 | benign | -0.435 | Destabilizing | 0.015 | N | 0.204 | neutral | None | None | None | None | N |
| V/K | 0.5881 | likely_pathogenic | 0.6185 | pathogenic | -0.921 | Destabilizing | 0.988 | D | 0.645 | neutral | None | None | None | None | N |
| V/L | 0.2315 | likely_benign | 0.2508 | benign | -0.435 | Destabilizing | 0.437 | N | 0.341 | neutral | N | 0.490097335 | None | None | N |
| V/M | 0.1628 | likely_benign | 0.1915 | benign | -0.445 | Destabilizing | 0.968 | D | 0.545 | neutral | N | 0.481421924 | None | None | N |
| V/N | 0.4101 | ambiguous | 0.4855 | ambiguous | -0.75 | Destabilizing | 0.996 | D | 0.689 | prob.neutral | None | None | None | None | N |
| V/P | 0.9579 | likely_pathogenic | 0.9555 | pathogenic | -0.587 | Destabilizing | 0.996 | D | 0.63 | neutral | None | None | None | None | N |
| V/Q | 0.4189 | ambiguous | 0.4648 | ambiguous | -0.927 | Destabilizing | 0.996 | D | 0.649 | neutral | None | None | None | None | N |
| V/R | 0.5537 | ambiguous | 0.5835 | pathogenic | -0.375 | Destabilizing | 0.996 | D | 0.688 | prob.neutral | None | None | None | None | N |
| V/S | 0.3741 | ambiguous | 0.4419 | ambiguous | -1.21 | Destabilizing | 0.988 | D | 0.599 | neutral | None | None | None | None | N |
| V/T | 0.3127 | likely_benign | 0.3784 | ambiguous | -1.138 | Destabilizing | 0.919 | D | 0.485 | neutral | None | None | None | None | N |
| V/W | 0.8644 | likely_pathogenic | 0.8962 | pathogenic | -0.902 | Destabilizing | 0.999 | D | 0.7 | prob.neutral | None | None | None | None | N |
| V/Y | 0.6202 | likely_pathogenic | 0.6641 | pathogenic | -0.613 | Destabilizing | 0.996 | D | 0.583 | 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.