Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 5941 | 18046;18047;18048 | chr2:178730712;178730711;178730710 | chr2:179595439;179595438;179595437 |
| N2AB | 5624 | 17095;17096;17097 | chr2:178730712;178730711;178730710 | chr2:179595439;179595438;179595437 |
| N2A | 4697 | 14314;14315;14316 | chr2:178730712;178730711;178730710 | chr2:179595439;179595438;179595437 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | rs372022675  |
-0.859 | 0.976 | N | 0.517 | 0.243 | None | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 6.47E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/M | rs372022675 |
-0.859 | 0.976 | N | 0.517 | 0.243 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/M | rs372022675 |
-0.859 | 0.976 | N | 0.517 | 0.243 | None | gnomAD-4.0.0 | 6.08953E-06 | None | None | None | None | N | None | 1.7466E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 6.02472E-06 | 0 | 0 |
| I/R | rs773190186 |
None | 0.035 | N | 0.469 | 0.342 | 0.642757676758 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07125E-04 | 0 |
| I/R | rs773190186 |
None | 0.035 | N | 0.469 | 0.342 | 0.642757676758 | gnomAD-4.0.0 | 6.5716E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.07125E-04 | 0 |
| I/T | rs773190186 |
-1.554 | 0.959 | N | 0.476 | 0.341 | 0.649000688064 | gnomAD-2.1.1 | 1.62E-05 | None | None | None | None | N | None | 0 | 5.8E-05 | None | 0 | 0 | None | 0 | None | 0 | 1.8E-05 | 0 |
| I/T | rs773190186 |
-1.554 | 0.959 | N | 0.476 | 0.341 | 0.649000688064 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs773190186 |
-1.554 | 0.959 | N | 0.476 | 0.341 | 0.649000688064 | gnomAD-4.0.0 | 6.19762E-06 | None | None | None | None | N | None | 0 | 5.00233E-05 | None | 0 | 0 | None | 1.56255E-05 | 0 | 2.54305E-06 | 1.0981E-05 | 3.20277E-05 |
| I/V | rs397517487 |
-1.299 | 0.509 | N | 0.302 | 0.145 | None | gnomAD-2.1.1 | 3.95E-05 | None | None | None | None | N | None | 2.06851E-04 | 1.13282E-04 | None | 0 | 0 | None | 0 | None | 0 | 7.9E-06 | 1.41044E-04 |
| I/V | rs397517487 |
-1.299 | 0.509 | N | 0.302 | 0.145 | None | gnomAD-3.1.2 | 6.57E-05 | None | None | None | None | N | None | 2.17119E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/V | rs397517487 |
-1.299 | 0.509 | N | 0.302 | 0.145 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| I/V | rs397517487 |
-1.299 | 0.509 | N | 0.302 | 0.145 | None | gnomAD-4.0.0 | 1.92111E-05 | None | None | None | None | N | None | 2.26564E-04 | 1.0001E-04 | None | 0 | 0 | None | 6.2498E-05 | 0 | 2.54307E-06 | 0 | 1.60077E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.4588 | ambiguous | 0.4525 | ambiguous | -2.059 | Highly Destabilizing | 0.927 | D | 0.475 | neutral | None | None | None | None | N |
| I/C | 0.8838 | likely_pathogenic | 0.8802 | pathogenic | -1.327 | Destabilizing | 0.999 | D | 0.53 | neutral | None | None | None | None | N |
| I/D | 0.8849 | likely_pathogenic | 0.8915 | pathogenic | -1.945 | Destabilizing | 0.991 | D | 0.618 | neutral | None | None | None | None | N |
| I/E | 0.7274 | likely_pathogenic | 0.7444 | pathogenic | -1.908 | Destabilizing | 0.982 | D | 0.614 | neutral | None | None | None | None | N |
| I/F | 0.2892 | likely_benign | 0.3039 | benign | -1.487 | Destabilizing | 0.982 | D | 0.495 | neutral | None | None | None | None | N |
| I/G | 0.8616 | likely_pathogenic | 0.8586 | pathogenic | -2.42 | Highly Destabilizing | 0.991 | D | 0.611 | neutral | None | None | None | None | N |
| I/H | 0.5982 | likely_pathogenic | 0.6221 | pathogenic | -1.635 | Destabilizing | 0.999 | D | 0.605 | neutral | None | None | None | None | N |
| I/K | 0.3889 | ambiguous | 0.4256 | ambiguous | -1.401 | Destabilizing | 0.852 | D | 0.585 | neutral | N | 0.365128762 | None | None | N |
| I/L | 0.1736 | likely_benign | 0.1716 | benign | -1.105 | Destabilizing | 0.005 | N | 0.141 | neutral | N | 0.437858439 | None | None | N |
| I/M | 0.1388 | likely_benign | 0.1396 | benign | -0.861 | Destabilizing | 0.976 | D | 0.517 | neutral | N | 0.48884462 | None | None | N |
| I/N | 0.5079 | ambiguous | 0.5406 | ambiguous | -1.31 | Destabilizing | 0.991 | D | 0.618 | neutral | None | None | None | None | N |
| I/P | 0.9543 | likely_pathogenic | 0.9546 | pathogenic | -1.396 | Destabilizing | 0.997 | D | 0.62 | neutral | None | None | None | None | N |
| I/Q | 0.5223 | ambiguous | 0.5451 | ambiguous | -1.495 | Destabilizing | 0.982 | D | 0.619 | neutral | None | None | None | None | N |
| I/R | 0.3079 | likely_benign | 0.3285 | benign | -0.791 | Destabilizing | 0.035 | N | 0.469 | neutral | N | 0.402436357 | None | None | N |
| I/S | 0.4656 | ambiguous | 0.486 | ambiguous | -1.935 | Destabilizing | 0.969 | D | 0.582 | neutral | None | None | None | None | N |
| I/T | 0.2301 | likely_benign | 0.2418 | benign | -1.787 | Destabilizing | 0.959 | D | 0.476 | neutral | N | 0.45780685 | None | None | N |
| I/V | 0.0987 | likely_benign | 0.1015 | benign | -1.396 | Destabilizing | 0.509 | D | 0.302 | neutral | N | 0.4518651 | None | None | N |
| I/W | 0.8464 | likely_pathogenic | 0.8409 | pathogenic | -1.622 | Destabilizing | 0.999 | D | 0.63 | neutral | None | None | None | None | N |
| I/Y | 0.6667 | likely_pathogenic | 0.6907 | pathogenic | -1.391 | Destabilizing | 0.997 | D | 0.563 | 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.