Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21449 | 64570;64571;64572 | chr2:178586556;178586555;178586554 | chr2:179451283;179451282;179451281 |
| N2AB | 19808 | 59647;59648;59649 | chr2:178586556;178586555;178586554 | chr2:179451283;179451282;179451281 |
| N2A | 18881 | 56866;56867;56868 | chr2:178586556;178586555;178586554 | chr2:179451283;179451282;179451281 |
| N2B | 12384 | 37375;37376;37377 | chr2:178586556;178586555;178586554 | chr2:179451283;179451282;179451281 |
| Novex-1 | 12509 | 37750;37751;37752 | chr2:178586556;178586555;178586554 | chr2:179451283;179451282;179451281 |
| Novex-2 | 12576 | 37951;37952;37953 | chr2:178586556;178586555;178586554 | chr2:179451283;179451282;179451281 |
| 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 | rs748888420  |
-1.712 | 0.91 | N | 0.575 | 0.103 | 0.505640481493 | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.35E-05 | 0 |
| V/A | rs748888420 |
-1.712 | 0.91 | N | 0.575 | 0.103 | 0.505640481493 | gnomAD-3.1.2 | 1.98E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| V/A | rs748888420 |
-1.712 | 0.91 | N | 0.575 | 0.103 | 0.505640481493 | gnomAD-4.0.0 | 6.4118E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.58102E-06 | 0 | 2.84657E-05 |
| V/I | rs2049029716 |
None | 0.248 | N | 0.309 | 0.053 | 0.323615622048 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs2049029716 |
None | 0.248 | N | 0.309 | 0.053 | 0.323615622048 | gnomAD-4.0.0 | 2.03005E-06 | None | None | None | None | I | None | 0 | 6.15612E-05 | None | 0 | 0 | None | 0 | 0 | 1.20497E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2261 | likely_benign | 0.1796 | benign | -1.232 | Destabilizing | 0.91 | D | 0.575 | neutral | N | 0.470684855 | None | None | I |
| V/C | 0.6759 | likely_pathogenic | 0.5953 | pathogenic | -0.861 | Destabilizing | 0.351 | N | 0.531 | neutral | None | None | None | None | I |
| V/D | 0.4989 | ambiguous | 0.4041 | ambiguous | -0.987 | Destabilizing | 0.994 | D | 0.781 | deleterious | N | 0.500218328 | None | None | I |
| V/E | 0.3339 | likely_benign | 0.2683 | benign | -1.062 | Destabilizing | 0.996 | D | 0.763 | deleterious | None | None | None | None | I |
| V/F | 0.2069 | likely_benign | 0.1835 | benign | -1.235 | Destabilizing | 0.989 | D | 0.687 | prob.neutral | N | 0.50452807 | None | None | I |
| V/G | 0.3246 | likely_benign | 0.2694 | benign | -1.459 | Destabilizing | 0.994 | D | 0.743 | deleterious | N | 0.474567881 | None | None | I |
| V/H | 0.6232 | likely_pathogenic | 0.5416 | ambiguous | -0.905 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | I |
| V/I | 0.0699 | likely_benign | 0.0712 | benign | -0.746 | Destabilizing | 0.248 | N | 0.309 | neutral | N | 0.440247305 | None | None | I |
| V/K | 0.3643 | ambiguous | 0.2835 | benign | -0.878 | Destabilizing | 0.996 | D | 0.761 | deleterious | None | None | None | None | I |
| V/L | 0.1942 | likely_benign | 0.1712 | benign | -0.746 | Destabilizing | 0.835 | D | 0.555 | neutral | N | 0.439015154 | None | None | I |
| V/M | 0.1564 | likely_benign | 0.1466 | benign | -0.496 | Destabilizing | 0.996 | D | 0.669 | neutral | None | None | None | None | I |
| V/N | 0.3295 | likely_benign | 0.2732 | benign | -0.586 | Destabilizing | 0.996 | D | 0.786 | deleterious | None | None | None | None | I |
| V/P | 0.5343 | ambiguous | 0.4634 | ambiguous | -0.872 | Destabilizing | 0.999 | D | 0.775 | deleterious | None | None | None | None | I |
| V/Q | 0.3459 | ambiguous | 0.2858 | benign | -0.883 | Destabilizing | 0.999 | D | 0.769 | deleterious | None | None | None | None | I |
| V/R | 0.3577 | ambiguous | 0.2783 | benign | -0.256 | Destabilizing | 0.996 | D | 0.787 | deleterious | None | None | None | None | I |
| V/S | 0.265 | likely_benign | 0.2141 | benign | -1.06 | Destabilizing | 0.942 | D | 0.719 | prob.delet. | None | None | None | None | I |
| V/T | 0.1893 | likely_benign | 0.1645 | benign | -1.034 | Destabilizing | 0.304 | N | 0.328 | neutral | None | None | None | None | I |
| V/W | 0.8123 | likely_pathogenic | 0.7652 | pathogenic | -1.287 | Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | I |
| V/Y | 0.5501 | ambiguous | 0.4634 | ambiguous | -1.013 | Destabilizing | 0.999 | D | 0.689 | prob.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.