Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28050 | 84373;84374;84375 | chr2:178561984;178561983;178561982 | chr2:179426711;179426710;179426709 |
| N2AB | 26409 | 79450;79451;79452 | chr2:178561984;178561983;178561982 | chr2:179426711;179426710;179426709 |
| N2A | 25482 | 76669;76670;76671 | chr2:178561984;178561983;178561982 | chr2:179426711;179426710;179426709 |
| N2B | 18985 | 57178;57179;57180 | chr2:178561984;178561983;178561982 | chr2:179426711;179426710;179426709 |
| Novex-1 | 19110 | 57553;57554;57555 | chr2:178561984;178561983;178561982 | chr2:179426711;179426710;179426709 |
| Novex-2 | 19177 | 57754;57755;57756 | chr2:178561984;178561983;178561982 | chr2:179426711;179426710;179426709 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | None | None | 0.012 | N | 0.521 | 0.339 | 0.670074228213 | gnomAD-4.0.0 | 1.59239E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43332E-05 | 0 |
| I/V | rs201348580  |
-1.517 | None | N | 0.215 | 0.051 | None | gnomAD-2.1.1 | 2.90083E-04 | None | None | None | None | N | None | 1.65371E-04 | 4.8227E-04 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 4.54873E-04 | 1.41363E-04 |
| I/V | rs201348580 |
-1.517 | None | N | 0.215 | 0.051 | None | gnomAD-3.1.2 | 4.20566E-04 | None | None | None | None | N | None | 2.17066E-04 | 7.20839E-04 | 0 | 0 | 0 | None | 0 | 0 | 6.32093E-04 | 2.07125E-04 | 0 |
| I/V | rs201348580 |
-1.517 | None | N | 0.215 | 0.051 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| I/V | rs201348580 |
-1.517 | None | N | 0.215 | 0.051 | None | gnomAD-4.0.0 | 7.0472E-04 | None | None | None | None | N | None | 2.39878E-04 | 5.83625E-04 | None | 0 | 0 | None | 0 | 0 | 8.8081E-04 | 1.09825E-04 | 5.60395E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.8451 | likely_pathogenic | 0.8461 | pathogenic | -2.678 | Highly Destabilizing | 0.007 | N | 0.404 | neutral | None | None | None | None | N |
| I/C | 0.9201 | likely_pathogenic | 0.9233 | pathogenic | -2.021 | Highly Destabilizing | 0.356 | N | 0.702 | prob.neutral | None | None | None | None | N |
| I/D | 0.9961 | likely_pathogenic | 0.997 | pathogenic | -3.17 | Highly Destabilizing | 0.356 | N | 0.746 | deleterious | None | None | None | None | N |
| I/E | 0.9923 | likely_pathogenic | 0.994 | pathogenic | -2.87 | Highly Destabilizing | 0.136 | N | 0.699 | prob.neutral | None | None | None | None | N |
| I/F | 0.5231 | ambiguous | 0.5554 | ambiguous | -1.562 | Destabilizing | 0.072 | N | 0.531 | neutral | None | None | None | None | N |
| I/G | 0.9721 | likely_pathogenic | 0.9753 | pathogenic | -3.295 | Highly Destabilizing | 0.136 | N | 0.677 | prob.neutral | None | None | None | None | N |
| I/H | 0.9884 | likely_pathogenic | 0.992 | pathogenic | -2.902 | Highly Destabilizing | 0.864 | D | 0.756 | deleterious | None | None | None | None | N |
| I/K | 0.9861 | likely_pathogenic | 0.9897 | pathogenic | -1.955 | Destabilizing | 0.106 | N | 0.711 | prob.delet. | N | 0.474609744 | None | None | N |
| I/L | 0.2173 | likely_benign | 0.2312 | benign | -0.847 | Destabilizing | 0.002 | N | 0.262 | neutral | N | 0.435544334 | None | None | N |
| I/M | 0.2947 | likely_benign | 0.2951 | benign | -0.997 | Destabilizing | 0.171 | N | 0.562 | neutral | N | 0.473849276 | None | None | N |
| I/N | 0.9551 | likely_pathogenic | 0.9675 | pathogenic | -2.536 | Highly Destabilizing | 0.628 | D | 0.761 | deleterious | None | None | None | None | N |
| I/P | 0.9819 | likely_pathogenic | 0.9875 | pathogenic | -1.444 | Destabilizing | 0.356 | N | 0.756 | deleterious | None | None | None | None | N |
| I/Q | 0.989 | likely_pathogenic | 0.9911 | pathogenic | -2.248 | Highly Destabilizing | 0.628 | D | 0.76 | deleterious | None | None | None | None | N |
| I/R | 0.9789 | likely_pathogenic | 0.9854 | pathogenic | -1.909 | Destabilizing | 0.295 | N | 0.764 | deleterious | N | 0.474609744 | None | None | N |
| I/S | 0.9403 | likely_pathogenic | 0.9495 | pathogenic | -3.217 | Highly Destabilizing | 0.072 | N | 0.645 | neutral | None | None | None | None | N |
| I/T | 0.8672 | likely_pathogenic | 0.8624 | pathogenic | -2.75 | Highly Destabilizing | 0.012 | N | 0.521 | neutral | N | 0.474609744 | None | None | N |
| I/V | 0.0579 | likely_benign | 0.0559 | benign | -1.444 | Destabilizing | None | N | 0.215 | neutral | N | 0.362890094 | None | None | N |
| I/W | 0.9898 | likely_pathogenic | 0.9916 | pathogenic | -1.997 | Destabilizing | 0.864 | D | 0.755 | deleterious | None | None | None | None | N |
| I/Y | 0.9455 | likely_pathogenic | 0.9624 | pathogenic | -1.728 | Destabilizing | 0.356 | N | 0.701 | prob.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.