Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33602 | 101029;101030;101031 | chr2:178535811;178535810;178535809 | chr2:179400538;179400537;179400536 |
| N2AB | 31961 | 96106;96107;96108 | chr2:178535811;178535810;178535809 | chr2:179400538;179400537;179400536 |
| N2A | 31034 | 93325;93326;93327 | chr2:178535811;178535810;178535809 | chr2:179400538;179400537;179400536 |
| N2B | 24537 | 73834;73835;73836 | chr2:178535811;178535810;178535809 | chr2:179400538;179400537;179400536 |
| Novex-1 | 24662 | 74209;74210;74211 | chr2:178535811;178535810;178535809 | chr2:179400538;179400537;179400536 |
| Novex-2 | 24729 | 74410;74411;74412 | chr2:178535811;178535810;178535809 | chr2:179400538;179400537;179400536 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/L | rs759368043  |
-0.412 | 0.283 | N | 0.256 | 0.225 | 0.402471007487 | gnomAD-2.1.1 | 4.09E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.6E-05 | None | 0 | None | 0 | 0 | 0 |
| M/L | rs759368043 |
-0.412 | 0.283 | N | 0.256 | 0.225 | 0.402471007487 | gnomAD-3.1.2 | 6.6E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.9425E-04 | None | 0 | 0 | 0 | 0 | 0 |
| M/L | rs759368043 |
-0.412 | 0.283 | N | 0.256 | 0.225 | 0.402471007487 | gnomAD-4.0.0 | 6.6031E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.9425E-04 | None | 0 | 0 | 0 | 0 | 0 |
| M/T | rs576732964 |
-0.447 | 0.781 | N | 0.347 | 0.196 | 0.634123272708 | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07555E-04 | 0 |
| M/T | rs576732964 |
-0.447 | 0.781 | N | 0.347 | 0.196 | 0.634123272708 | gnomAD-4.0.0 | 6.84198E-06 | None | None | None | None | N | None | 0 | 1.676E-05 | None | 0 | 0 | None | 0 | 0 | 3.39877E-06 | 6.61492E-05 | 0 |
| M/V | rs759368043 |
None | 0.67 | N | 0.481 | 0.273 | 0.332646915603 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| M/V | rs759368043 |
None | 0.67 | N | 0.481 | 0.273 | 0.332646915603 | gnomAD-4.0.0 | 2.48992E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.54985E-06 | 1.10307E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.4511 | ambiguous | 0.45 | ambiguous | -0.195 | Destabilizing | 0.762 | D | 0.399 | neutral | None | None | None | None | N |
| M/C | 0.7878 | likely_pathogenic | 0.7625 | pathogenic | -0.456 | Destabilizing | 0.998 | D | 0.407 | neutral | None | None | None | None | N |
| M/D | 0.7573 | likely_pathogenic | 0.7709 | pathogenic | 0.395 | Stabilizing | 0.943 | D | 0.469 | neutral | None | None | None | None | N |
| M/E | 0.5057 | ambiguous | 0.5138 | ambiguous | 0.332 | Stabilizing | 0.484 | N | 0.379 | neutral | None | None | None | None | N |
| M/F | 0.3828 | ambiguous | 0.3296 | benign | -0.268 | Destabilizing | 0.887 | D | 0.431 | neutral | None | None | None | None | N |
| M/G | 0.637 | likely_pathogenic | 0.631 | pathogenic | -0.256 | Destabilizing | 0.94 | D | 0.427 | neutral | None | None | None | None | N |
| M/H | 0.5495 | ambiguous | 0.5603 | ambiguous | 0.3 | Stabilizing | 0.996 | D | 0.451 | neutral | None | None | None | None | N |
| M/I | 0.4701 | ambiguous | 0.4407 | ambiguous | -0.131 | Destabilizing | 0.87 | D | 0.47 | neutral | N | 0.46380645 | None | None | N |
| M/K | 0.1852 | likely_benign | 0.2415 | benign | 0.376 | Stabilizing | 0.014 | N | 0.209 | neutral | N | 0.4648466 | None | None | N |
| M/L | 0.1787 | likely_benign | 0.1645 | benign | -0.131 | Destabilizing | 0.283 | N | 0.256 | neutral | N | 0.430189735 | None | None | N |
| M/N | 0.4983 | ambiguous | 0.5063 | ambiguous | 0.493 | Stabilizing | 0.943 | D | 0.445 | neutral | None | None | None | None | N |
| M/P | 0.6767 | likely_pathogenic | 0.698 | pathogenic | -0.132 | Destabilizing | 0.981 | D | 0.447 | neutral | None | None | None | None | N |
| M/Q | 0.2674 | likely_benign | 0.2878 | benign | 0.363 | Stabilizing | 0.763 | D | 0.403 | neutral | None | None | None | None | N |
| M/R | 0.245 | likely_benign | 0.2839 | benign | 0.726 | Stabilizing | 0.538 | D | 0.371 | neutral | N | 0.483432361 | None | None | N |
| M/S | 0.4595 | ambiguous | 0.4639 | ambiguous | 0.1 | Stabilizing | 0.886 | D | 0.389 | neutral | None | None | None | None | N |
| M/T | 0.3103 | likely_benign | 0.3288 | benign | 0.118 | Stabilizing | 0.781 | D | 0.347 | neutral | N | 0.45345617 | None | None | N |
| M/V | 0.1521 | likely_benign | 0.1556 | benign | -0.132 | Destabilizing | 0.67 | D | 0.481 | neutral | N | 0.457957913 | None | None | N |
| M/W | 0.6879 | likely_pathogenic | 0.665 | pathogenic | -0.292 | Destabilizing | 0.999 | D | 0.427 | neutral | None | None | None | None | N |
| M/Y | 0.6206 | likely_pathogenic | 0.5749 | pathogenic | -0.086 | Destabilizing | 0.989 | D | 0.431 | 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.