Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33668 | 101227;101228;101229 | chr2:178535613;178535612;178535611 | chr2:179400340;179400339;179400338 |
| N2AB | 32027 | 96304;96305;96306 | chr2:178535613;178535612;178535611 | chr2:179400340;179400339;179400338 |
| N2A | 31100 | 93523;93524;93525 | chr2:178535613;178535612;178535611 | chr2:179400340;179400339;179400338 |
| N2B | 24603 | 74032;74033;74034 | chr2:178535613;178535612;178535611 | chr2:179400340;179400339;179400338 |
| Novex-1 | 24728 | 74407;74408;74409 | chr2:178535613;178535612;178535611 | chr2:179400340;179400339;179400338 |
| Novex-2 | 24795 | 74608;74609;74610 | chr2:178535613;178535612;178535611 | chr2:179400340;179400339;179400338 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs372534712  |
None | 0.936 | N | 0.538 | 0.262 | None | gnomAD-4.0.0 | 4.78951E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.29628E-06 | 0 | 0 |
| V/E | None | None | 0.99 | N | 0.595 | 0.445 | 0.578293158758 | gnomAD-4.0.0 | 6.84215E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99468E-07 | 0 | 0 |
| V/M | rs1417934977 |
-0.739 | 0.994 | N | 0.529 | 0.184 | 0.241078983079 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| V/M | rs1417934977 |
-0.739 | 0.994 | N | 0.529 | 0.184 | 0.241078983079 | gnomAD-4.0.0 | 1.59129E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8583E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.6027 | likely_pathogenic | 0.3755 | ambiguous | -1.831 | Destabilizing | 0.936 | D | 0.538 | neutral | N | 0.491225125 | None | None | N |
| V/C | 0.9225 | likely_pathogenic | 0.8574 | pathogenic | -1.474 | Destabilizing | 1.0 | D | 0.57 | neutral | None | None | None | None | N |
| V/D | 0.9253 | likely_pathogenic | 0.7714 | pathogenic | -2.0 | Highly Destabilizing | 0.999 | D | 0.674 | neutral | None | None | None | None | N |
| V/E | 0.8182 | likely_pathogenic | 0.6139 | pathogenic | -1.921 | Destabilizing | 0.99 | D | 0.595 | neutral | N | 0.42909923 | None | None | N |
| V/F | 0.5327 | ambiguous | 0.3379 | benign | -1.258 | Destabilizing | 0.997 | D | 0.561 | neutral | None | None | None | None | N |
| V/G | 0.7784 | likely_pathogenic | 0.5547 | ambiguous | -2.242 | Highly Destabilizing | 0.999 | D | 0.631 | neutral | N | 0.510773677 | None | None | N |
| V/H | 0.9006 | likely_pathogenic | 0.7715 | pathogenic | -1.787 | Destabilizing | 1.0 | D | 0.72 | prob.delet. | None | None | None | None | N |
| V/I | 0.0816 | likely_benign | 0.0787 | benign | -0.756 | Destabilizing | 0.01 | N | 0.25 | neutral | None | None | None | None | N |
| V/K | 0.8324 | likely_pathogenic | 0.6227 | pathogenic | -1.489 | Destabilizing | 0.997 | D | 0.603 | neutral | None | None | None | None | N |
| V/L | 0.409 | ambiguous | 0.2981 | benign | -0.756 | Destabilizing | 0.333 | N | 0.469 | neutral | N | 0.450301222 | None | None | N |
| V/M | 0.2796 | likely_benign | 0.2014 | benign | -0.717 | Destabilizing | 0.994 | D | 0.529 | neutral | N | 0.462211726 | None | None | N |
| V/N | 0.7228 | likely_pathogenic | 0.5208 | ambiguous | -1.464 | Destabilizing | 0.977 | D | 0.691 | prob.neutral | None | None | None | None | N |
| V/P | 0.9948 | likely_pathogenic | 0.9888 | pathogenic | -1.082 | Destabilizing | 0.992 | D | 0.633 | neutral | None | None | None | None | N |
| V/Q | 0.7485 | likely_pathogenic | 0.5617 | ambiguous | -1.549 | Destabilizing | 0.998 | D | 0.661 | neutral | None | None | None | None | N |
| V/R | 0.7705 | likely_pathogenic | 0.5472 | ambiguous | -1.06 | Destabilizing | 0.998 | D | 0.712 | prob.delet. | None | None | None | None | N |
| V/S | 0.6504 | likely_pathogenic | 0.4198 | ambiguous | -2.069 | Highly Destabilizing | 0.959 | D | 0.558 | neutral | None | None | None | None | N |
| V/T | 0.3807 | ambiguous | 0.2338 | benign | -1.867 | Destabilizing | 0.203 | N | 0.453 | neutral | None | None | None | None | N |
| V/W | 0.974 | likely_pathogenic | 0.9291 | pathogenic | -1.548 | Destabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | N |
| V/Y | 0.8954 | likely_pathogenic | 0.7581 | pathogenic | -1.233 | Destabilizing | 0.999 | D | 0.572 | 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.