Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24381 | 73366;73367;73368 | chr2:178572991;178572990;178572989 | chr2:179437718;179437717;179437716 |
| N2AB | 22740 | 68443;68444;68445 | chr2:178572991;178572990;178572989 | chr2:179437718;179437717;179437716 |
| N2A | 21813 | 65662;65663;65664 | chr2:178572991;178572990;178572989 | chr2:179437718;179437717;179437716 |
| N2B | 15316 | 46171;46172;46173 | chr2:178572991;178572990;178572989 | chr2:179437718;179437717;179437716 |
| Novex-1 | 15441 | 46546;46547;46548 | chr2:178572991;178572990;178572989 | chr2:179437718;179437717;179437716 |
| Novex-2 | 15508 | 46747;46748;46749 | chr2:178572991;178572990;178572989 | chr2:179437718;179437717;179437716 |
| 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/S | rs762504227  |
-0.664 | 1.0 | N | 0.536 | 0.23 | 0.26547132957 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| A/S | rs762504227 |
-0.664 | 1.0 | N | 0.536 | 0.23 | 0.26547132957 | gnomAD-4.0.0 | 1.59288E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43369E-05 | 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 | 0.4282 | ambiguous | 0.4335 | ambiguous | -0.584 | Destabilizing | 1.0 | D | 0.712 | prob.delet. | None | None | None | None | I |
| A/D | 0.2331 | likely_benign | 0.2586 | benign | -0.211 | Destabilizing | 1.0 | D | 0.782 | deleterious | None | None | None | None | I |
| A/E | 0.248 | likely_benign | 0.2665 | benign | -0.199 | Destabilizing | 1.0 | D | 0.773 | deleterious | N | 0.449464221 | None | None | I |
| A/F | 0.3838 | ambiguous | 0.4049 | ambiguous | -0.553 | Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | I |
| A/G | 0.0944 | likely_benign | 0.108 | benign | -0.759 | Destabilizing | 1.0 | D | 0.537 | neutral | N | 0.436212496 | None | None | I |
| A/H | 0.5031 | ambiguous | 0.5204 | ambiguous | -0.596 | Destabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | None | I |
| A/I | 0.2492 | likely_benign | 0.2589 | benign | 0.03 | Stabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | I |
| A/K | 0.4507 | ambiguous | 0.473 | ambiguous | -0.554 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | I |
| A/L | 0.1959 | likely_benign | 0.2022 | benign | 0.03 | Stabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | I |
| A/M | 0.2164 | likely_benign | 0.22 | benign | -0.263 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | I |
| A/N | 0.1751 | likely_benign | 0.184 | benign | -0.434 | Destabilizing | 1.0 | D | 0.8 | deleterious | None | None | None | None | I |
| A/P | 0.3504 | ambiguous | 0.3772 | ambiguous | -0.11 | Destabilizing | 1.0 | D | 0.774 | deleterious | N | 0.488676572 | None | None | I |
| A/Q | 0.3334 | likely_benign | 0.3547 | ambiguous | -0.457 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | I |
| A/R | 0.4769 | ambiguous | 0.4897 | ambiguous | -0.376 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | I |
| A/S | 0.0897 | likely_benign | 0.0956 | benign | -0.851 | Destabilizing | 1.0 | D | 0.536 | neutral | N | 0.464281745 | None | None | I |
| A/T | 0.0903 | likely_benign | 0.091 | benign | -0.715 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | N | 0.46466296 | None | None | I |
| A/V | 0.1288 | likely_benign | 0.1314 | benign | -0.11 | Destabilizing | 1.0 | D | 0.624 | neutral | N | 0.46201223 | None | None | I |
| A/W | 0.7803 | likely_pathogenic | 0.794 | pathogenic | -0.866 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | I |
| A/Y | 0.451 | ambiguous | 0.4743 | ambiguous | -0.413 | Destabilizing | 1.0 | D | 0.783 | deleterious | 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.