Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21110 | 63553;63554;63555 | chr2:178588079;178588078;178588077 | chr2:179452806;179452805;179452804 |
| N2AB | 19469 | 58630;58631;58632 | chr2:178588079;178588078;178588077 | chr2:179452806;179452805;179452804 |
| N2A | 18542 | 55849;55850;55851 | chr2:178588079;178588078;178588077 | chr2:179452806;179452805;179452804 |
| N2B | 12045 | 36358;36359;36360 | chr2:178588079;178588078;178588077 | chr2:179452806;179452805;179452804 |
| Novex-1 | 12170 | 36733;36734;36735 | chr2:178588079;178588078;178588077 | chr2:179452806;179452805;179452804 |
| Novex-2 | 12237 | 36934;36935;36936 | chr2:178588079;178588078;178588077 | chr2:179452806;179452805;179452804 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/E | None | None | 0.002 | N | 0.245 | 0.103 | 0.163833314356 | gnomAD-4.0.0 | 1.36913E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79962E-06 | 0 | 0 |
| A/G | rs370687831  |
-0.318 | 0.058 | N | 0.381 | 0.041 | 0.12205267543 | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.14E-05 | 0 |
| A/G | rs370687831 |
-0.318 | 0.058 | N | 0.381 | 0.041 | 0.12205267543 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| A/G | rs370687831 |
-0.318 | 0.058 | N | 0.381 | 0.041 | 0.12205267543 | gnomAD-4.0.0 | 8.06084E-06 | None | None | None | None | N | None | 0 | 1.6685E-05 | None | 0 | 0 | None | 0 | 0 | 1.01755E-05 | 0 | 0 |
| A/T | None | None | None | N | 0.262 | 0.101 | 0.124217242631 | 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 |
| A/V | rs370687831 |
-0.133 | 0.064 | N | 0.38 | 0.049 | None | gnomAD-2.1.1 | 1.36044E-04 | None | None | None | None | N | None | 4.14E-05 | 8.5E-05 | None | 0 | 0 | None | 0 | None | 0 | 2.66629E-04 | 0 |
| A/V | rs370687831 |
-0.133 | 0.064 | N | 0.38 | 0.049 | None | gnomAD-3.1.2 | 8.56E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.4715E-04 | 2.07211E-04 | 0 |
| A/V | rs370687831 |
-0.133 | 0.064 | N | 0.38 | 0.049 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| A/V | rs370687831 |
-0.133 | 0.064 | N | 0.38 | 0.049 | None | gnomAD-4.0.0 | 1.22144E-04 | None | None | None | None | N | None | 5.33575E-05 | 5.00384E-05 | None | 0 | 0 | None | 0 | 0 | 1.55177E-04 | 3.2954E-05 | 6.40697E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.2551 | likely_benign | 0.246 | benign | -0.679 | Destabilizing | 0.676 | D | 0.412 | neutral | None | None | None | None | N |
| A/D | 0.1294 | likely_benign | 0.1312 | benign | -0.58 | Destabilizing | None | N | 0.175 | neutral | None | None | None | None | N |
| A/E | 0.1255 | likely_benign | 0.127 | benign | -0.743 | Destabilizing | 0.002 | N | 0.245 | neutral | N | 0.424605849 | None | None | N |
| A/F | 0.1946 | likely_benign | 0.1954 | benign | -1.03 | Destabilizing | 0.214 | N | 0.434 | neutral | None | None | None | None | N |
| A/G | 0.0859 | likely_benign | 0.0845 | benign | -0.383 | Destabilizing | 0.058 | N | 0.381 | neutral | N | 0.425819357 | None | None | N |
| A/H | 0.2006 | likely_benign | 0.1989 | benign | -0.536 | Destabilizing | 0.628 | D | 0.434 | neutral | None | None | None | None | N |
| A/I | 0.1151 | likely_benign | 0.1178 | benign | -0.413 | Destabilizing | 0.038 | N | 0.373 | neutral | None | None | None | None | N |
| A/K | 0.1424 | likely_benign | 0.1463 | benign | -0.64 | Destabilizing | None | N | 0.338 | neutral | None | None | None | None | N |
| A/L | 0.0988 | likely_benign | 0.0976 | benign | -0.413 | Destabilizing | 0.006 | N | 0.396 | neutral | None | None | None | None | N |
| A/M | 0.1272 | likely_benign | 0.1276 | benign | -0.335 | Destabilizing | 0.001 | N | 0.365 | neutral | None | None | None | None | N |
| A/N | 0.1236 | likely_benign | 0.1203 | benign | -0.269 | Destabilizing | 0.072 | N | 0.393 | neutral | None | None | None | None | N |
| A/P | 0.1219 | likely_benign | 0.1291 | benign | -0.354 | Destabilizing | 0.106 | N | 0.4 | neutral | N | 0.475594816 | None | None | N |
| A/Q | 0.15 | likely_benign | 0.1474 | benign | -0.583 | Destabilizing | 0.072 | N | 0.368 | neutral | None | None | None | None | N |
| A/R | 0.1577 | likely_benign | 0.155 | benign | -0.181 | Destabilizing | 0.038 | N | 0.377 | neutral | None | None | None | None | N |
| A/S | 0.0756 | likely_benign | 0.0725 | benign | -0.436 | Destabilizing | 0.012 | N | 0.439 | neutral | N | 0.443538326 | None | None | N |
| A/T | 0.0633 | likely_benign | 0.0633 | benign | -0.528 | Destabilizing | None | N | 0.262 | neutral | N | 0.493660502 | None | None | N |
| A/V | 0.074 | likely_benign | 0.0743 | benign | -0.354 | Destabilizing | 0.064 | N | 0.38 | neutral | N | 0.408967179 | None | None | N |
| A/W | 0.4285 | ambiguous | 0.4269 | ambiguous | -1.168 | Destabilizing | 0.864 | D | 0.46 | neutral | None | None | None | None | N |
| A/Y | 0.2344 | likely_benign | 0.2367 | benign | -0.817 | Destabilizing | 0.356 | N | 0.425 | 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.