Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15215 | 45868;45869;45870 | chr2:178620967;178620966;178620965 | chr2:179485694;179485693;179485692 |
| N2AB | 13574 | 40945;40946;40947 | chr2:178620967;178620966;178620965 | chr2:179485694;179485693;179485692 |
| N2A | 12647 | 38164;38165;38166 | chr2:178620967;178620966;178620965 | chr2:179485694;179485693;179485692 |
| N2B | 6150 | 18673;18674;18675 | chr2:178620967;178620966;178620965 | chr2:179485694;179485693;179485692 |
| Novex-1 | 6275 | 19048;19049;19050 | chr2:178620967;178620966;178620965 | chr2:179485694;179485693;179485692 |
| Novex-2 | 6342 | 19249;19250;19251 | chr2:178620967;178620966;178620965 | chr2:179485694;179485693;179485692 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/E | None | None | 0.698 | N | 0.58 | 0.287 | 0.368743488249 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| K/T | rs374244504  |
0.172 | 0.822 | D | 0.587 | 0.525 | None | gnomAD-2.1.1 | 1.22E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.69E-05 | 0 |
| K/T | rs374244504 |
0.172 | 0.822 | D | 0.587 | 0.525 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.95E-05 | 0 | 0 |
| K/T | rs374244504 |
0.172 | 0.822 | D | 0.587 | 0.525 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| K/T | rs374244504 |
0.172 | 0.822 | D | 0.587 | 0.525 | None | gnomAD-4.0.0 | 5.13608E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.58929E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.5088 | ambiguous | 0.5112 | ambiguous | -0.067 | Destabilizing | 0.754 | D | 0.565 | neutral | None | None | None | None | I |
| K/C | 0.8465 | likely_pathogenic | 0.8412 | pathogenic | -0.292 | Destabilizing | 0.998 | D | 0.682 | prob.neutral | None | None | None | None | I |
| K/D | 0.7472 | likely_pathogenic | 0.752 | pathogenic | 0.071 | Stabilizing | 0.754 | D | 0.582 | neutral | None | None | None | None | I |
| K/E | 0.1963 | likely_benign | 0.202 | benign | 0.119 | Stabilizing | 0.698 | D | 0.58 | neutral | N | 0.507678386 | None | None | I |
| K/F | 0.8748 | likely_pathogenic | 0.8797 | pathogenic | -0.059 | Destabilizing | 0.993 | D | 0.659 | neutral | None | None | None | None | I |
| K/G | 0.6418 | likely_pathogenic | 0.6443 | pathogenic | -0.329 | Destabilizing | 0.754 | D | 0.534 | neutral | None | None | None | None | I |
| K/H | 0.425 | ambiguous | 0.4124 | ambiguous | -0.583 | Destabilizing | 0.978 | D | 0.646 | neutral | None | None | None | None | I |
| K/I | 0.4934 | ambiguous | 0.5086 | ambiguous | 0.561 | Stabilizing | 0.978 | D | 0.678 | prob.neutral | None | None | None | None | I |
| K/L | 0.5141 | ambiguous | 0.5147 | ambiguous | 0.561 | Stabilizing | 0.956 | D | 0.54 | neutral | None | None | None | None | I |
| K/M | 0.3652 | ambiguous | 0.3719 | ambiguous | 0.196 | Stabilizing | 0.992 | D | 0.63 | neutral | D | 0.64615057 | None | None | I |
| K/N | 0.5351 | ambiguous | 0.5314 | ambiguous | 0.029 | Stabilizing | 0.032 | N | 0.263 | neutral | D | 0.561747918 | None | None | I |
| K/P | 0.8724 | likely_pathogenic | 0.8911 | pathogenic | 0.381 | Stabilizing | 0.978 | D | 0.654 | neutral | None | None | None | None | I |
| K/Q | 0.1569 | likely_benign | 0.1523 | benign | -0.063 | Destabilizing | 0.126 | N | 0.243 | neutral | N | 0.516383448 | None | None | I |
| K/R | 0.0935 | likely_benign | 0.0937 | benign | -0.203 | Destabilizing | 0.698 | D | 0.555 | neutral | N | 0.515251275 | None | None | I |
| K/S | 0.5691 | likely_pathogenic | 0.5561 | ambiguous | -0.464 | Destabilizing | 0.754 | D | 0.544 | neutral | None | None | None | None | I |
| K/T | 0.256 | likely_benign | 0.2605 | benign | -0.246 | Destabilizing | 0.822 | D | 0.587 | neutral | D | 0.53727196 | None | None | I |
| K/V | 0.4731 | ambiguous | 0.485 | ambiguous | 0.381 | Stabilizing | 0.956 | D | 0.579 | neutral | None | None | None | None | I |
| K/W | 0.8611 | likely_pathogenic | 0.8735 | pathogenic | -0.06 | Destabilizing | 0.998 | D | 0.682 | prob.neutral | None | None | None | None | I |
| K/Y | 0.7846 | likely_pathogenic | 0.7928 | pathogenic | 0.267 | Stabilizing | 0.978 | D | 0.66 | neutral | None | None | None | None | I |
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.