Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24488 | 73687;73688;73689 | chr2:178572670;178572669;178572668 | chr2:179437397;179437396;179437395 |
| N2AB | 22847 | 68764;68765;68766 | chr2:178572670;178572669;178572668 | chr2:179437397;179437396;179437395 |
| N2A | 21920 | 65983;65984;65985 | chr2:178572670;178572669;178572668 | chr2:179437397;179437396;179437395 |
| N2B | 15423 | 46492;46493;46494 | chr2:178572670;178572669;178572668 | chr2:179437397;179437396;179437395 |
| Novex-1 | 15548 | 46867;46868;46869 | chr2:178572670;178572669;178572668 | chr2:179437397;179437396;179437395 |
| Novex-2 | 15615 | 47068;47069;47070 | chr2:178572670;178572669;178572668 | chr2:179437397;179437396;179437395 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/K | rs1223093442  |
None | 1.0 | N | 0.719 | 0.285 | 0.203808441222 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| N/K | rs1223093442 |
None | 1.0 | N | 0.719 | 0.285 | 0.203808441222 | gnomAD-4.0.0 | 6.57566E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47089E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.3399 | likely_benign | 0.3552 | ambiguous | -0.294 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | N |
| N/C | 0.4056 | ambiguous | 0.4229 | ambiguous | 0.511 | Stabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| N/D | 0.122 | likely_benign | 0.1272 | benign | -0.095 | Destabilizing | 0.999 | D | 0.6 | neutral | N | 0.508965523 | None | None | N |
| N/E | 0.3774 | ambiguous | 0.3862 | ambiguous | -0.135 | Destabilizing | 0.999 | D | 0.712 | prob.delet. | None | None | None | None | N |
| N/F | 0.7124 | likely_pathogenic | 0.7248 | pathogenic | -0.654 | Destabilizing | 1.0 | D | 0.738 | prob.delet. | None | None | None | None | N |
| N/G | 0.3563 | ambiguous | 0.3847 | ambiguous | -0.467 | Destabilizing | 0.999 | D | 0.572 | neutral | None | None | None | None | N |
| N/H | 0.1565 | likely_benign | 0.1571 | benign | -0.541 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | N | 0.487246724 | None | None | N |
| N/I | 0.4699 | ambiguous | 0.4687 | ambiguous | 0.08 | Stabilizing | 1.0 | D | 0.768 | deleterious | N | 0.499781571 | None | None | N |
| N/K | 0.4156 | ambiguous | 0.4228 | ambiguous | 0.132 | Stabilizing | 1.0 | D | 0.719 | prob.delet. | N | 0.51585421 | None | None | N |
| N/L | 0.4325 | ambiguous | 0.444 | ambiguous | 0.08 | Stabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| N/M | 0.4724 | ambiguous | 0.4792 | ambiguous | 0.57 | Stabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| N/P | 0.7408 | likely_pathogenic | 0.7527 | pathogenic | -0.019 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| N/Q | 0.3943 | ambiguous | 0.4084 | ambiguous | -0.295 | Destabilizing | 1.0 | D | 0.702 | prob.neutral | None | None | None | None | N |
| N/R | 0.4939 | ambiguous | 0.5116 | ambiguous | 0.238 | Stabilizing | 1.0 | D | 0.732 | prob.delet. | None | None | None | None | N |
| N/S | 0.1109 | likely_benign | 0.1138 | benign | -0.019 | Destabilizing | 0.999 | D | 0.555 | neutral | N | 0.461492239 | None | None | N |
| N/T | 0.2301 | likely_benign | 0.2263 | benign | 0.072 | Stabilizing | 0.999 | D | 0.709 | prob.delet. | N | 0.483625873 | None | None | N |
| N/V | 0.4448 | ambiguous | 0.4458 | ambiguous | -0.019 | Destabilizing | 1.0 | D | 0.746 | deleterious | None | None | None | None | N |
| N/W | 0.8744 | likely_pathogenic | 0.8824 | pathogenic | -0.635 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| N/Y | 0.2786 | likely_benign | 0.2919 | benign | -0.371 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | N | 0.499274592 | 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.