Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2586 | 7981;7982;7983 | chr2:178773208;178773207;178773206 | chr2:179637935;179637934;179637933 |
| N2AB | 2586 | 7981;7982;7983 | chr2:178773208;178773207;178773206 | chr2:179637935;179637934;179637933 |
| N2A | 2586 | 7981;7982;7983 | chr2:178773208;178773207;178773206 | chr2:179637935;179637934;179637933 |
| N2B | 2540 | 7843;7844;7845 | chr2:178773208;178773207;178773206 | chr2:179637935;179637934;179637933 |
| Novex-1 | 2540 | 7843;7844;7845 | chr2:178773208;178773207;178773206 | chr2:179637935;179637934;179637933 |
| Novex-2 | 2540 | 7843;7844;7845 | chr2:178773208;178773207;178773206 | chr2:179637935;179637934;179637933 |
| Novex-3 | 2586 | 7981;7982;7983 | chr2:178773208;178773207;178773206 | chr2:179637935;179637934;179637933 |
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/L | None | None | 0.509 | N | 0.263 | 0.239 | 0.512424132817 | gnomAD-4.0.0 | 1.59126E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43349E-05 | 0 |
| I/M | rs556000493  |
-0.862 | 0.988 | N | 0.512 | 0.26 | None | gnomAD-2.1.1 | 2.95773E-04 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 2.38734E-03 | None | 0 | 8.84E-06 | 0 |
| I/M | rs556000493 |
-0.862 | 0.988 | N | 0.512 | 0.26 | None | gnomAD-3.1.2 | 5.91E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 1.657E-03 | 0 |
| I/M | rs556000493 |
-0.862 | 0.988 | N | 0.512 | 0.26 | None | 1000 genomes | 7.98722E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 4.1E-03 | None |
| I/M | rs556000493 |
-0.862 | 0.988 | N | 0.512 | 0.26 | None | gnomAD-4.0.0 | 1.25169E-04 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.78022E-06 | 2.0319E-03 | 1.44028E-04 |
| I/V | rs2091789026 |
None | 0.061 | N | 0.119 | 0.139 | 0.490352026379 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/V | rs2091789026 |
None | 0.061 | N | 0.119 | 0.139 | 0.490352026379 | gnomAD-4.0.0 | 6.57091E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.4699E-05 | 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 | 0.4182 | ambiguous | 0.3698 | ambiguous | -2.14 | Highly Destabilizing | 0.079 | N | 0.191 | neutral | None | None | None | None | N |
| I/C | 0.6477 | likely_pathogenic | 0.608 | pathogenic | -1.255 | Destabilizing | 0.999 | D | 0.553 | neutral | None | None | None | None | N |
| I/D | 0.6473 | likely_pathogenic | 0.5798 | pathogenic | -1.801 | Destabilizing | 0.991 | D | 0.638 | neutral | None | None | None | None | N |
| I/E | 0.5162 | ambiguous | 0.4613 | ambiguous | -1.716 | Destabilizing | 0.939 | D | 0.635 | neutral | None | None | None | None | N |
| I/F | 0.1716 | likely_benign | 0.1497 | benign | -1.319 | Destabilizing | 0.991 | D | 0.5 | neutral | None | None | None | None | N |
| I/G | 0.6795 | likely_pathogenic | 0.6364 | pathogenic | -2.554 | Highly Destabilizing | 0.939 | D | 0.63 | neutral | None | None | None | None | N |
| I/H | 0.3585 | ambiguous | 0.3102 | benign | -1.759 | Destabilizing | 0.1 | N | 0.468 | neutral | None | None | None | None | N |
| I/K | 0.2577 | likely_benign | 0.2217 | benign | -1.513 | Destabilizing | 0.92 | D | 0.641 | neutral | N | 0.454284187 | None | None | N |
| I/L | 0.149 | likely_benign | 0.1411 | benign | -1.015 | Destabilizing | 0.509 | D | 0.263 | neutral | N | 0.499667311 | None | None | N |
| I/M | 0.1191 | likely_benign | 0.1292 | benign | -0.778 | Destabilizing | 0.988 | D | 0.512 | neutral | N | 0.514543533 | None | None | N |
| I/N | 0.1712 | likely_benign | 0.1478 | benign | -1.44 | Destabilizing | 0.982 | D | 0.642 | neutral | None | None | None | None | N |
| I/P | 0.9549 | likely_pathogenic | 0.9409 | pathogenic | -1.364 | Destabilizing | 0.991 | D | 0.648 | neutral | None | None | None | None | N |
| I/Q | 0.3639 | ambiguous | 0.3275 | benign | -1.534 | Destabilizing | 0.991 | D | 0.665 | neutral | None | None | None | None | N |
| I/R | 0.2059 | likely_benign | 0.1741 | benign | -0.962 | Destabilizing | 0.976 | D | 0.648 | neutral | N | 0.497147967 | None | None | N |
| I/S | 0.279 | likely_benign | 0.2409 | benign | -2.128 | Highly Destabilizing | 0.884 | D | 0.62 | neutral | None | None | None | None | N |
| I/T | 0.2024 | likely_benign | 0.1752 | benign | -1.925 | Destabilizing | 0.92 | D | 0.533 | neutral | N | 0.463041295 | None | None | N |
| I/V | 0.0961 | likely_benign | 0.0899 | benign | -1.364 | Destabilizing | 0.061 | N | 0.119 | neutral | N | 0.415130834 | None | None | N |
| I/W | 0.7275 | likely_pathogenic | 0.6712 | pathogenic | -1.502 | Destabilizing | 0.999 | D | 0.664 | neutral | None | None | None | None | N |
| I/Y | 0.3501 | ambiguous | 0.3261 | benign | -1.284 | Destabilizing | 0.982 | D | 0.581 | 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.