Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 6877 | 20854;20855;20856 | chr2:178725575;178725574;178725573 | chr2:179590302;179590301;179590300 |
| N2AB | 6560 | 19903;19904;19905 | chr2:178725575;178725574;178725573 | chr2:179590302;179590301;179590300 |
| N2A | 5633 | 17122;17123;17124 | chr2:178725575;178725574;178725573 | chr2:179590302;179590301;179590300 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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/L | None | None | 0.002 | N | 0.242 | 0.199 | 0.247322355667 | gnomAD-4.0.0 | 2.73887E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59954E-06 | 0 | 0 |
| I/M | rs1227070261  |
-1.258 | 0.81 | N | 0.697 | 0.386 | 0.394536629495 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.58E-05 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs142794598 |
-2.823 | 0.549 | N | 0.715 | 0.4 | None | gnomAD-2.1.1 | 3.5868E-04 | None | None | None | None | N | None | 3.72794E-03 | 2.27609E-04 | None | 0 | 0 | None | 0 | None | 0 | 7.85E-06 | 1.41683E-04 |
| I/T | rs142794598 |
-2.823 | 0.549 | N | 0.715 | 0.4 | None | gnomAD-3.1.2 | 1.01932E-03 | None | None | None | None | N | None | 3.57298E-03 | 3.93494E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.78011E-04 |
| I/T | rs142794598 |
-2.823 | 0.549 | N | 0.715 | 0.4 | None | 1000 genomes | 1.99681E-03 | None | None | None | None | N | None | 7.6E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| I/T | rs142794598 |
-2.823 | 0.549 | N | 0.715 | 0.4 | None | gnomAD-4.0.0 | 1.80456E-04 | None | None | None | None | N | None | 3.48316E-03 | 2.3377E-04 | None | 0 | 0 | None | 0 | 1.65508E-04 | 5.93619E-06 | 0 | 1.28139E-04 |
| I/V | rs1023569847 |
None | 0.001 | N | 0.223 | 0.164 | 0.233150807113 | gnomAD-4.0.0 | 1.36944E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99884E-07 | 0 | 1.65772E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.4032 | ambiguous | 0.3491 | ambiguous | -2.343 | Highly Destabilizing | 0.25 | N | 0.66 | neutral | None | None | None | None | N |
| I/C | 0.8438 | likely_pathogenic | 0.8286 | pathogenic | -1.532 | Destabilizing | 0.977 | D | 0.769 | deleterious | None | None | None | None | N |
| I/D | 0.989 | likely_pathogenic | 0.9906 | pathogenic | -2.742 | Highly Destabilizing | 0.972 | D | 0.826 | deleterious | None | None | None | None | N |
| I/E | 0.9696 | likely_pathogenic | 0.9726 | pathogenic | -2.436 | Highly Destabilizing | 0.92 | D | 0.806 | deleterious | None | None | None | None | N |
| I/F | 0.3593 | ambiguous | 0.3573 | ambiguous | -1.366 | Destabilizing | 0.85 | D | 0.758 | deleterious | None | None | None | None | N |
| I/G | 0.9104 | likely_pathogenic | 0.8986 | pathogenic | -2.955 | Highly Destabilizing | 0.92 | D | 0.801 | deleterious | None | None | None | None | N |
| I/H | 0.9621 | likely_pathogenic | 0.9674 | pathogenic | -2.641 | Highly Destabilizing | 0.992 | D | 0.803 | deleterious | None | None | None | None | N |
| I/K | 0.9431 | likely_pathogenic | 0.9514 | pathogenic | -1.624 | Destabilizing | 0.896 | D | 0.806 | deleterious | D | 0.522922613 | None | None | N |
| I/L | 0.2068 | likely_benign | 0.1813 | benign | -0.532 | Destabilizing | 0.002 | N | 0.242 | neutral | N | 0.516727442 | None | None | N |
| I/M | 0.1918 | likely_benign | 0.1533 | benign | -0.638 | Destabilizing | 0.81 | D | 0.697 | prob.neutral | N | 0.504311379 | None | None | N |
| I/N | 0.9103 | likely_pathogenic | 0.9231 | pathogenic | -2.223 | Highly Destabilizing | 0.972 | D | 0.83 | deleterious | None | None | None | None | N |
| I/P | 0.9584 | likely_pathogenic | 0.9565 | pathogenic | -1.121 | Destabilizing | 0.972 | D | 0.828 | deleterious | None | None | None | None | N |
| I/Q | 0.9451 | likely_pathogenic | 0.9478 | pathogenic | -1.904 | Destabilizing | 0.972 | D | 0.825 | deleterious | None | None | None | None | N |
| I/R | 0.9025 | likely_pathogenic | 0.9172 | pathogenic | -1.683 | Destabilizing | 0.896 | D | 0.83 | deleterious | D | 0.522922613 | None | None | N |
| I/S | 0.7018 | likely_pathogenic | 0.6801 | pathogenic | -2.879 | Highly Destabilizing | 0.85 | D | 0.775 | deleterious | None | None | None | None | N |
| I/T | 0.2759 | likely_benign | 0.2468 | benign | -2.403 | Highly Destabilizing | 0.549 | D | 0.715 | prob.delet. | N | 0.509791881 | None | None | N |
| I/V | 0.0556 | likely_benign | 0.0549 | benign | -1.121 | Destabilizing | 0.001 | N | 0.223 | neutral | N | 0.411703627 | None | None | N |
| I/W | 0.9631 | likely_pathogenic | 0.9604 | pathogenic | -1.797 | Destabilizing | 0.992 | D | 0.805 | deleterious | None | None | None | None | N |
| I/Y | 0.8907 | likely_pathogenic | 0.901 | pathogenic | -1.469 | Destabilizing | 0.92 | D | 0.795 | 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.