Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26380 | 79363;79364;79365 | chr2:178566994;178566993;178566992 | chr2:179431721;179431720;179431719 |
| N2AB | 24739 | 74440;74441;74442 | chr2:178566994;178566993;178566992 | chr2:179431721;179431720;179431719 |
| N2A | 23812 | 71659;71660;71661 | chr2:178566994;178566993;178566992 | chr2:179431721;179431720;179431719 |
| N2B | 17315 | 52168;52169;52170 | chr2:178566994;178566993;178566992 | chr2:179431721;179431720;179431719 |
| Novex-1 | 17440 | 52543;52544;52545 | chr2:178566994;178566993;178566992 | chr2:179431721;179431720;179431719 |
| Novex-2 | 17507 | 52744;52745;52746 | chr2:178566994;178566993;178566992 | chr2:179431721;179431720;179431719 |
| 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/I | rs755474723  |
-0.25 | 0.126 | N | 0.189 | 0.192 | 0.347438807231 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.67E-05 | 0 |
| M/I | rs755474723 |
-0.25 | 0.126 | N | 0.189 | 0.192 | 0.347438807231 | gnomAD-4.0.0 | 6.36641E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.14365E-05 | 0 | 0 |
| M/T | None | None | 0.956 | N | 0.438 | 0.421 | 0.7112413483 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.5626 | ambiguous | 0.5334 | ambiguous | -2.1 | Highly Destabilizing | 0.923 | D | 0.489 | neutral | None | None | None | None | N |
| M/C | 0.77 | likely_pathogenic | 0.7623 | pathogenic | -2.495 | Highly Destabilizing | 0.999 | D | 0.5 | neutral | None | None | None | None | N |
| M/D | 0.999 | likely_pathogenic | 0.9984 | pathogenic | -2.521 | Highly Destabilizing | 0.997 | D | 0.597 | neutral | None | None | None | None | N |
| M/E | 0.9889 | likely_pathogenic | 0.9854 | pathogenic | -2.331 | Highly Destabilizing | 0.997 | D | 0.496 | neutral | None | None | None | None | N |
| M/F | 0.8919 | likely_pathogenic | 0.8676 | pathogenic | -0.729 | Destabilizing | 0.967 | D | 0.498 | neutral | None | None | None | None | N |
| M/G | 0.9614 | likely_pathogenic | 0.9559 | pathogenic | -2.49 | Highly Destabilizing | 0.997 | D | 0.541 | neutral | None | None | None | None | N |
| M/H | 0.9919 | likely_pathogenic | 0.99 | pathogenic | -2.166 | Highly Destabilizing | 0.999 | D | 0.523 | neutral | None | None | None | None | N |
| M/I | 0.672 | likely_pathogenic | 0.5141 | ambiguous | -0.992 | Destabilizing | 0.126 | N | 0.189 | neutral | N | 0.466180325 | None | None | N |
| M/K | 0.973 | likely_pathogenic | 0.9664 | pathogenic | -1.552 | Destabilizing | 0.985 | D | 0.547 | neutral | N | 0.506085508 | None | None | N |
| M/L | 0.4237 | ambiguous | 0.3526 | ambiguous | -0.992 | Destabilizing | 0.296 | N | 0.23 | neutral | N | 0.468353839 | None | None | N |
| M/N | 0.9819 | likely_pathogenic | 0.9734 | pathogenic | -1.907 | Destabilizing | 0.997 | D | 0.561 | neutral | None | None | None | None | N |
| M/P | 0.9714 | likely_pathogenic | 0.956 | pathogenic | -1.345 | Destabilizing | 0.997 | D | 0.554 | neutral | None | None | None | None | N |
| M/Q | 0.8923 | likely_pathogenic | 0.8892 | pathogenic | -1.666 | Destabilizing | 0.997 | D | 0.516 | neutral | None | None | None | None | N |
| M/R | 0.9671 | likely_pathogenic | 0.9599 | pathogenic | -1.599 | Destabilizing | 0.996 | D | 0.581 | neutral | N | 0.477135094 | None | None | N |
| M/S | 0.8711 | likely_pathogenic | 0.8375 | pathogenic | -2.347 | Highly Destabilizing | 0.989 | D | 0.475 | neutral | None | None | None | None | N |
| M/T | 0.8531 | likely_pathogenic | 0.7812 | pathogenic | -2.051 | Highly Destabilizing | 0.956 | D | 0.438 | neutral | N | 0.443092822 | None | None | N |
| M/V | 0.2845 | likely_benign | 0.1911 | benign | -1.345 | Destabilizing | 0.493 | N | 0.384 | neutral | N | 0.444380901 | None | None | N |
| M/W | 0.994 | likely_pathogenic | 0.9928 | pathogenic | -1.107 | Destabilizing | 0.999 | D | 0.52 | neutral | None | None | None | None | N |
| M/Y | 0.9911 | likely_pathogenic | 0.9887 | pathogenic | -1.058 | Destabilizing | 0.997 | D | 0.571 | 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.