Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17782 | 53569;53570;53571 | chr2:178607258;178607257;178607256 | chr2:179471985;179471984;179471983 |
| N2AB | 16141 | 48646;48647;48648 | chr2:178607258;178607257;178607256 | chr2:179471985;179471984;179471983 |
| N2A | 15214 | 45865;45866;45867 | chr2:178607258;178607257;178607256 | chr2:179471985;179471984;179471983 |
| N2B | 8717 | 26374;26375;26376 | chr2:178607258;178607257;178607256 | chr2:179471985;179471984;179471983 |
| Novex-1 | 8842 | 26749;26750;26751 | chr2:178607258;178607257;178607256 | chr2:179471985;179471984;179471983 |
| Novex-2 | 8909 | 26950;26951;26952 | chr2:178607258;178607257;178607256 | chr2:179471985;179471984;179471983 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/V | rs1178247710  |
-1.366 | 0.704 | N | 0.482 | 0.1 | 0.422883881359 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| L/V | rs1178247710 |
-1.366 | 0.704 | N | 0.482 | 0.1 | 0.422883881359 | 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 |
| L/V | rs1178247710 |
-1.366 | 0.704 | N | 0.482 | 0.1 | 0.422883881359 | gnomAD-4.0.0 | 6.20081E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.47969E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.6734 | likely_pathogenic | 0.8406 | pathogenic | -2.314 | Highly Destabilizing | 0.939 | D | 0.444 | neutral | None | None | None | None | N |
| L/C | 0.8205 | likely_pathogenic | 0.9066 | pathogenic | -1.474 | Destabilizing | 0.999 | D | 0.503 | neutral | None | None | None | None | N |
| L/D | 0.9798 | likely_pathogenic | 0.9938 | pathogenic | -2.51 | Highly Destabilizing | 0.991 | D | 0.585 | neutral | None | None | None | None | N |
| L/E | 0.8839 | likely_pathogenic | 0.9627 | pathogenic | -2.45 | Highly Destabilizing | 0.991 | D | 0.587 | neutral | None | None | None | None | N |
| L/F | 0.3193 | likely_benign | 0.4955 | ambiguous | -1.581 | Destabilizing | 0.046 | N | 0.246 | neutral | None | None | None | None | N |
| L/G | 0.9291 | likely_pathogenic | 0.9694 | pathogenic | -2.704 | Highly Destabilizing | 0.991 | D | 0.573 | neutral | None | None | None | None | N |
| L/H | 0.6479 | likely_pathogenic | 0.8396 | pathogenic | -1.991 | Destabilizing | 0.999 | D | 0.609 | neutral | None | None | None | None | N |
| L/I | 0.156 | likely_benign | 0.2557 | benign | -1.251 | Destabilizing | 0.852 | D | 0.462 | neutral | N | 0.426398147 | None | None | N |
| L/K | 0.7794 | likely_pathogenic | 0.9099 | pathogenic | -1.777 | Destabilizing | 0.991 | D | 0.567 | neutral | None | None | None | None | N |
| L/M | 0.1554 | likely_benign | 0.2467 | benign | -0.938 | Destabilizing | 0.579 | D | 0.408 | neutral | None | None | None | None | N |
| L/N | 0.8071 | likely_pathogenic | 0.9205 | pathogenic | -1.719 | Destabilizing | 0.991 | D | 0.59 | neutral | None | None | None | None | N |
| L/P | 0.9882 | likely_pathogenic | 0.9931 | pathogenic | -1.581 | Destabilizing | 0.996 | D | 0.606 | neutral | N | 0.47844312 | None | None | N |
| L/Q | 0.507 | ambiguous | 0.7687 | pathogenic | -1.863 | Destabilizing | 0.988 | D | 0.581 | neutral | N | 0.42687815 | None | None | N |
| L/R | 0.7048 | likely_pathogenic | 0.8506 | pathogenic | -1.145 | Destabilizing | 0.988 | D | 0.567 | neutral | N | 0.433862837 | None | None | N |
| L/S | 0.7232 | likely_pathogenic | 0.8945 | pathogenic | -2.299 | Highly Destabilizing | 0.884 | D | 0.498 | neutral | None | None | None | None | N |
| L/T | 0.5112 | ambiguous | 0.7455 | pathogenic | -2.131 | Highly Destabilizing | 0.17 | N | 0.337 | neutral | None | None | None | None | N |
| L/V | 0.1909 | likely_benign | 0.3122 | benign | -1.581 | Destabilizing | 0.704 | D | 0.482 | neutral | N | 0.413967567 | None | None | N |
| L/W | 0.7185 | likely_pathogenic | 0.8348 | pathogenic | -1.804 | Destabilizing | 0.999 | D | 0.583 | neutral | None | None | None | None | N |
| L/Y | 0.6867 | likely_pathogenic | 0.8338 | pathogenic | -1.606 | Destabilizing | 0.964 | D | 0.507 | 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.