Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17381 | 52366;52367;52368 | chr2:178608870;178608869;178608868 | chr2:179473597;179473596;179473595 |
| N2AB | 15740 | 47443;47444;47445 | chr2:178608870;178608869;178608868 | chr2:179473597;179473596;179473595 |
| N2A | 14813 | 44662;44663;44664 | chr2:178608870;178608869;178608868 | chr2:179473597;179473596;179473595 |
| N2B | 8316 | 25171;25172;25173 | chr2:178608870;178608869;178608868 | chr2:179473597;179473596;179473595 |
| Novex-1 | 8441 | 25546;25547;25548 | chr2:178608870;178608869;178608868 | chr2:179473597;179473596;179473595 |
| Novex-2 | 8508 | 25747;25748;25749 | chr2:178608870;178608869;178608868 | chr2:179473597;179473596;179473595 |
| 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 | rs2154197961  |
None | 0.004 | N | 0.213 | 0.201 | 0.170165803431 | gnomAD-4.0.0 | 3.19387E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.78056E-05 | None | 0 | 0 | 0 | 0 | 3.03104E-05 |
| I/T | rs775637498 |
-1.604 | 0.117 | D | 0.341 | 0.316 | 0.578326236229 | gnomAD-2.1.1 | 1.44E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.14E-05 | 0 |
| I/T | rs775637498 |
-1.604 | 0.117 | D | 0.341 | 0.316 | 0.578326236229 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| I/T | rs775637498 |
-1.604 | 0.117 | D | 0.341 | 0.316 | 0.578326236229 | gnomAD-4.0.0 | 7.4477E-06 | None | None | None | None | N | None | 1.33711E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 9.32861E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.4533 | ambiguous | 0.3555 | ambiguous | -2.208 | Highly Destabilizing | 0.035 | N | 0.36 | neutral | None | None | None | None | N |
| I/C | 0.6572 | likely_pathogenic | 0.5746 | pathogenic | -1.562 | Destabilizing | 0.824 | D | 0.305 | neutral | None | None | None | None | N |
| I/D | 0.8392 | likely_pathogenic | 0.7513 | pathogenic | -2.017 | Highly Destabilizing | 0.555 | D | 0.443 | neutral | None | None | None | None | N |
| I/E | 0.6444 | likely_pathogenic | 0.5598 | ambiguous | -1.951 | Destabilizing | 0.555 | D | 0.43 | neutral | None | None | None | None | N |
| I/F | 0.2741 | likely_benign | 0.2263 | benign | -1.564 | Destabilizing | 0.317 | N | 0.37 | neutral | N | 0.490415 | None | None | N |
| I/G | 0.7468 | likely_pathogenic | 0.6146 | pathogenic | -2.614 | Highly Destabilizing | 0.38 | N | 0.439 | neutral | None | None | None | None | N |
| I/H | 0.6793 | likely_pathogenic | 0.5743 | pathogenic | -1.887 | Destabilizing | 0.935 | D | 0.385 | neutral | None | None | None | None | N |
| I/K | 0.4543 | ambiguous | 0.3755 | ambiguous | -1.587 | Destabilizing | 0.38 | N | 0.438 | neutral | None | None | None | None | N |
| I/L | 0.148 | likely_benign | 0.1183 | benign | -1.114 | Destabilizing | None | N | 0.069 | neutral | N | 0.506168439 | None | None | N |
| I/M | 0.1399 | likely_benign | 0.1202 | benign | -0.921 | Destabilizing | 0.004 | N | 0.213 | neutral | N | 0.498871243 | None | None | N |
| I/N | 0.4444 | ambiguous | 0.3323 | benign | -1.533 | Destabilizing | 0.484 | N | 0.436 | neutral | N | 0.50946708 | None | None | N |
| I/P | 0.7379 | likely_pathogenic | 0.6376 | pathogenic | -1.452 | Destabilizing | 0.791 | D | 0.445 | neutral | None | None | None | None | N |
| I/Q | 0.5399 | ambiguous | 0.4437 | ambiguous | -1.661 | Destabilizing | 0.38 | N | 0.435 | neutral | None | None | None | None | N |
| I/R | 0.4243 | ambiguous | 0.3293 | benign | -1.028 | Destabilizing | 0.38 | N | 0.446 | neutral | None | None | None | None | N |
| I/S | 0.437 | ambiguous | 0.3169 | benign | -2.209 | Highly Destabilizing | 0.117 | N | 0.38 | neutral | N | 0.475487069 | None | None | N |
| I/T | 0.2604 | likely_benign | 0.212 | benign | -2.016 | Highly Destabilizing | 0.117 | N | 0.341 | neutral | D | 0.522137969 | None | None | N |
| I/V | 0.0716 | likely_benign | 0.0678 | benign | -1.452 | Destabilizing | None | N | 0.068 | neutral | N | 0.436767069 | None | None | N |
| I/W | 0.8566 | likely_pathogenic | 0.812 | pathogenic | -1.724 | Destabilizing | 0.935 | D | 0.453 | neutral | None | None | None | None | N |
| I/Y | 0.657 | likely_pathogenic | 0.548 | ambiguous | -1.49 | Destabilizing | 0.555 | D | 0.352 | 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.