Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28564 | 85915;85916;85917 | chr2:178560442;178560441;178560440 | chr2:179425169;179425168;179425167 |
| N2AB | 26923 | 80992;80993;80994 | chr2:178560442;178560441;178560440 | chr2:179425169;179425168;179425167 |
| N2A | 25996 | 78211;78212;78213 | chr2:178560442;178560441;178560440 | chr2:179425169;179425168;179425167 |
| N2B | 19499 | 58720;58721;58722 | chr2:178560442;178560441;178560440 | chr2:179425169;179425168;179425167 |
| Novex-1 | 19624 | 59095;59096;59097 | chr2:178560442;178560441;178560440 | chr2:179425169;179425168;179425167 |
| Novex-2 | 19691 | 59296;59297;59298 | chr2:178560442;178560441;178560440 | chr2:179425169;179425168;179425167 |
| 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 | rs755352127  |
-0.24 | 0.007 | N | 0.101 | 0.153 | 0.225215365344 | gnomAD-2.1.1 | 4.03E-05 | None | None | None | None | N | None | 0 | 2.61643E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.66279E-04 |
| K/E | rs755352127 |
-0.24 | 0.007 | N | 0.101 | 0.153 | 0.225215365344 | gnomAD-4.0.0 | 1.91007E-05 | None | None | None | None | N | None | 0 | 2.74449E-04 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| K/I | rs199859344 |
0.412 | 0.939 | N | 0.502 | 0.376 | None | gnomAD-2.1.1 | 5.86678E-04 | None | None | None | None | N | None | 6.28151E-03 | 2.55377E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 4.22654E-04 |
| K/I | rs199859344 |
0.412 | 0.939 | N | 0.502 | 0.376 | None | gnomAD-3.1.2 | 1.6957E-03 | None | None | None | None | N | None | 6.0802E-03 | 1.31096E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.91388E-03 |
| K/I | rs199859344 |
0.412 | 0.939 | N | 0.502 | 0.376 | None | 1000 genomes | 2.59585E-03 | None | None | None | None | N | None | 9.8E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| K/I | rs199859344 |
0.412 | 0.939 | N | 0.502 | 0.376 | None | gnomAD-4.0.0 | 3.31552E-04 | None | None | None | None | N | None | 6.47689E-03 | 3.0008E-04 | None | 0 | 0 | None | 1.56348E-05 | 0 | 2.54288E-06 | 0 | 4.32277E-04 |
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 | 0.4774 | ambiguous | 0.4784 | ambiguous | -0.259 | Destabilizing | 0.373 | N | 0.403 | neutral | None | None | None | None | N |
| K/C | 0.7686 | likely_pathogenic | 0.7869 | pathogenic | -0.365 | Destabilizing | 0.996 | D | 0.491 | neutral | None | None | None | None | N |
| K/D | 0.8704 | likely_pathogenic | 0.8756 | pathogenic | -0.364 | Destabilizing | 0.59 | D | 0.351 | neutral | None | None | None | None | N |
| K/E | 0.4232 | ambiguous | 0.4418 | ambiguous | -0.342 | Destabilizing | 0.007 | N | 0.101 | neutral | N | 0.512494192 | None | None | N |
| K/F | 0.9583 | likely_pathogenic | 0.9588 | pathogenic | -0.478 | Destabilizing | 0.984 | D | 0.491 | neutral | None | None | None | None | N |
| K/G | 0.456 | ambiguous | 0.472 | ambiguous | -0.517 | Destabilizing | 0.742 | D | 0.411 | neutral | None | None | None | None | N |
| K/H | 0.515 | ambiguous | 0.5059 | ambiguous | -1.01 | Destabilizing | 0.953 | D | 0.395 | neutral | None | None | None | None | N |
| K/I | 0.8427 | likely_pathogenic | 0.7744 | pathogenic | 0.357 | Stabilizing | 0.939 | D | 0.502 | neutral | N | 0.503893992 | None | None | N |
| K/L | 0.7271 | likely_pathogenic | 0.7266 | pathogenic | 0.357 | Stabilizing | 0.742 | D | 0.428 | neutral | None | None | None | None | N |
| K/M | 0.5204 | ambiguous | 0.5511 | ambiguous | 0.484 | Stabilizing | 0.996 | D | 0.387 | neutral | None | None | None | None | N |
| K/N | 0.7446 | likely_pathogenic | 0.7428 | pathogenic | -0.088 | Destabilizing | 0.684 | D | 0.314 | neutral | N | 0.465657565 | None | None | N |
| K/P | 0.8772 | likely_pathogenic | 0.8771 | pathogenic | 0.181 | Stabilizing | 0.953 | D | 0.4 | neutral | None | None | None | None | N |
| K/Q | 0.2289 | likely_benign | 0.2265 | benign | -0.396 | Destabilizing | 0.521 | D | 0.42 | neutral | N | 0.477204908 | None | None | N |
| K/R | 0.0802 | likely_benign | 0.0804 | benign | -0.21 | Destabilizing | 0.684 | D | 0.363 | neutral | N | 0.480539276 | None | None | N |
| K/S | 0.5494 | ambiguous | 0.5568 | ambiguous | -0.635 | Destabilizing | 0.045 | N | 0.091 | neutral | None | None | None | None | N |
| K/T | 0.4774 | ambiguous | 0.4887 | ambiguous | -0.451 | Destabilizing | 0.521 | D | 0.373 | neutral | N | 0.476164497 | None | None | N |
| K/V | 0.7335 | likely_pathogenic | 0.7358 | pathogenic | 0.181 | Stabilizing | 0.854 | D | 0.414 | neutral | None | None | None | None | N |
| K/W | 0.9161 | likely_pathogenic | 0.9267 | pathogenic | -0.389 | Destabilizing | 0.996 | D | 0.615 | neutral | None | None | None | None | N |
| K/Y | 0.8764 | likely_pathogenic | 0.8821 | pathogenic | -0.009 | Destabilizing | 0.984 | D | 0.462 | 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.