Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26496 | 79711;79712;79713 | chr2:178566646;178566645;178566644 | chr2:179431373;179431372;179431371 |
| N2AB | 24855 | 74788;74789;74790 | chr2:178566646;178566645;178566644 | chr2:179431373;179431372;179431371 |
| N2A | 23928 | 72007;72008;72009 | chr2:178566646;178566645;178566644 | chr2:179431373;179431372;179431371 |
| N2B | 17431 | 52516;52517;52518 | chr2:178566646;178566645;178566644 | chr2:179431373;179431372;179431371 |
| Novex-1 | 17556 | 52891;52892;52893 | chr2:178566646;178566645;178566644 | chr2:179431373;179431372;179431371 |
| Novex-2 | 17623 | 53092;53093;53094 | chr2:178566646;178566645;178566644 | chr2:179431373;179431372;179431371 |
| 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/L | None | None | None | N | 0.159 | 0.12 | 0.0401082797425 | gnomAD-4.0.0 | 6.84576E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99536E-07 | 0 | 0 |
| I/T | rs749600987  |
-1.416 | None | N | 0.321 | 0.17 | 0.344945010812 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 1.15888E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs749600987 |
-1.416 | None | N | 0.321 | 0.17 | 0.344945010812 | gnomAD-4.0.0 | 4.10748E-06 | None | None | None | None | N | None | 0 | 8.94494E-05 | None | 0 | 0 | None | 0 | 0 | 1.79909E-06 | 0 | 0 |
| I/V | rs757760643 |
-0.836 | None | N | 0.145 | 0.135 | 0.0666544352282 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| I/V | rs757760643 |
-0.836 | None | N | 0.145 | 0.135 | 0.0666544352282 | gnomAD-4.0.0 | 2.7383E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.89732E-05 | 0 | 8.99536E-07 | 2.31873E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.184 | likely_benign | 0.1199 | benign | -2.169 | Highly Destabilizing | None | N | 0.308 | neutral | None | None | None | None | N |
| I/C | 0.5097 | ambiguous | 0.4435 | ambiguous | -1.148 | Destabilizing | 0.356 | N | 0.562 | neutral | None | None | None | None | N |
| I/D | 0.8282 | likely_pathogenic | 0.7252 | pathogenic | -2.046 | Highly Destabilizing | 0.072 | N | 0.632 | neutral | None | None | None | None | N |
| I/E | 0.737 | likely_pathogenic | 0.6189 | pathogenic | -1.975 | Destabilizing | 0.072 | N | 0.575 | neutral | None | None | None | None | N |
| I/F | 0.2126 | likely_benign | 0.1717 | benign | -1.478 | Destabilizing | 0.029 | N | 0.546 | neutral | N | 0.510648752 | None | None | N |
| I/G | 0.628 | likely_pathogenic | 0.4584 | ambiguous | -2.569 | Highly Destabilizing | 0.038 | N | 0.517 | neutral | None | None | None | None | N |
| I/H | 0.6569 | likely_pathogenic | 0.5623 | ambiguous | -1.86 | Destabilizing | 0.864 | D | 0.541 | neutral | None | None | None | None | N |
| I/K | 0.5744 | likely_pathogenic | 0.4948 | ambiguous | -1.671 | Destabilizing | 0.072 | N | 0.569 | neutral | None | None | None | None | N |
| I/L | 0.1213 | likely_benign | 0.1096 | benign | -1.088 | Destabilizing | None | N | 0.159 | neutral | N | 0.478845765 | None | None | N |
| I/M | 0.1172 | likely_benign | 0.0987 | benign | -0.717 | Destabilizing | 0.171 | N | 0.555 | neutral | N | 0.481221061 | None | None | N |
| I/N | 0.4649 | ambiguous | 0.3581 | ambiguous | -1.554 | Destabilizing | 0.171 | N | 0.64 | neutral | N | 0.49712327 | None | None | N |
| I/P | 0.5151 | ambiguous | 0.3826 | ambiguous | -1.422 | Destabilizing | 0.136 | N | 0.649 | neutral | None | None | None | None | N |
| I/Q | 0.6138 | likely_pathogenic | 0.5096 | ambiguous | -1.662 | Destabilizing | 0.356 | N | 0.625 | neutral | None | None | None | None | N |
| I/R | 0.4939 | ambiguous | 0.4092 | ambiguous | -1.079 | Destabilizing | 0.214 | N | 0.641 | neutral | None | None | None | None | N |
| I/S | 0.3111 | likely_benign | 0.2181 | benign | -2.138 | Highly Destabilizing | 0.012 | N | 0.407 | neutral | N | 0.478258546 | None | None | N |
| I/T | 0.1328 | likely_benign | 0.0992 | benign | -1.948 | Destabilizing | None | N | 0.321 | neutral | N | 0.520156457 | None | None | N |
| I/V | 0.0514 | likely_benign | 0.0501 | benign | -1.422 | Destabilizing | None | N | 0.145 | neutral | N | 0.377774694 | None | None | N |
| I/W | 0.8223 | likely_pathogenic | 0.7465 | pathogenic | -1.688 | Destabilizing | 0.864 | D | 0.528 | neutral | None | None | None | None | N |
| I/Y | 0.6119 | likely_pathogenic | 0.5252 | ambiguous | -1.465 | Destabilizing | 0.356 | N | 0.637 | 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.