Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28058 | 84397;84398;84399 | chr2:178561960;178561959;178561958 | chr2:179426687;179426686;179426685 |
| N2AB | 26417 | 79474;79475;79476 | chr2:178561960;178561959;178561958 | chr2:179426687;179426686;179426685 |
| N2A | 25490 | 76693;76694;76695 | chr2:178561960;178561959;178561958 | chr2:179426687;179426686;179426685 |
| N2B | 18993 | 57202;57203;57204 | chr2:178561960;178561959;178561958 | chr2:179426687;179426686;179426685 |
| Novex-1 | 19118 | 57577;57578;57579 | chr2:178561960;178561959;178561958 | chr2:179426687;179426686;179426685 |
| Novex-2 | 19185 | 57778;57779;57780 | chr2:178561960;178561959;178561958 | chr2:179426687;179426686;179426685 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/R | rs1293214241  |
-0.035 | 1.0 | D | 0.908 | 0.492 | 0.520161069619 | 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 |
| P/R | rs1293214241 |
-0.035 | 1.0 | D | 0.908 | 0.492 | 0.520161069619 | gnomAD-4.0.0 | 3.18617E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.72384E-06 | 0 | 0 |
| P/S | None | None | 1.0 | N | 0.84 | 0.359 | 0.38225645794 | gnomAD-4.0.0 | 1.59313E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.862E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.095 | likely_benign | 0.0893 | benign | -1.215 | Destabilizing | 1.0 | D | 0.826 | deleterious | N | 0.467931609 | None | None | N |
| P/C | 0.4805 | ambiguous | 0.4514 | ambiguous | -1.052 | Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | None | N |
| P/D | 0.6319 | likely_pathogenic | 0.5372 | ambiguous | -1.341 | Destabilizing | 1.0 | D | 0.844 | deleterious | None | None | None | None | N |
| P/E | 0.3575 | ambiguous | 0.3075 | benign | -1.419 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| P/F | 0.4865 | ambiguous | 0.4214 | ambiguous | -1.369 | Destabilizing | 1.0 | D | 0.909 | deleterious | None | None | None | None | N |
| P/G | 0.4792 | ambiguous | 0.4387 | ambiguous | -1.408 | Destabilizing | 1.0 | D | 0.881 | deleterious | None | None | None | None | N |
| P/H | 0.2619 | likely_benign | 0.2307 | benign | -0.879 | Destabilizing | 1.0 | D | 0.888 | deleterious | D | 0.542005513 | None | None | N |
| P/I | 0.2644 | likely_benign | 0.2166 | benign | -0.815 | Destabilizing | 1.0 | D | 0.903 | deleterious | None | None | None | None | N |
| P/K | 0.2951 | likely_benign | 0.2415 | benign | -0.848 | Destabilizing | 1.0 | D | 0.844 | deleterious | None | None | None | None | N |
| P/L | 0.1425 | likely_benign | 0.1219 | benign | -0.815 | Destabilizing | 1.0 | D | 0.893 | deleterious | D | 0.535168658 | None | None | N |
| P/M | 0.3171 | likely_benign | 0.2654 | benign | -0.593 | Destabilizing | 1.0 | D | 0.884 | deleterious | None | None | None | None | N |
| P/N | 0.4544 | ambiguous | 0.3734 | ambiguous | -0.674 | Destabilizing | 1.0 | D | 0.907 | deleterious | None | None | None | None | N |
| P/Q | 0.1908 | likely_benign | 0.1712 | benign | -1.016 | Destabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | None | N |
| P/R | 0.2284 | likely_benign | 0.2033 | benign | -0.255 | Destabilizing | 1.0 | D | 0.908 | deleterious | D | 0.529128271 | None | None | N |
| P/S | 0.17 | likely_benign | 0.1538 | benign | -1.092 | Destabilizing | 1.0 | D | 0.84 | deleterious | N | 0.506642696 | None | None | N |
| P/T | 0.1526 | likely_benign | 0.1348 | benign | -1.077 | Destabilizing | 1.0 | D | 0.839 | deleterious | D | 0.529888739 | None | None | N |
| P/V | 0.1996 | likely_benign | 0.1703 | benign | -0.915 | Destabilizing | 1.0 | D | 0.891 | deleterious | None | None | None | None | N |
| P/W | 0.7748 | likely_pathogenic | 0.7458 | pathogenic | -1.41 | Destabilizing | 1.0 | D | 0.887 | deleterious | None | None | None | None | N |
| P/Y | 0.515 | ambiguous | 0.4421 | ambiguous | -1.098 | Destabilizing | 1.0 | D | 0.917 | deleterious | 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.