Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27182 | 81769;81770;81771 | chr2:178564588;178564587;178564586 | chr2:179429315;179429314;179429313 |
| N2AB | 25541 | 76846;76847;76848 | chr2:178564588;178564587;178564586 | chr2:179429315;179429314;179429313 |
| N2A | 24614 | 74065;74066;74067 | chr2:178564588;178564587;178564586 | chr2:179429315;179429314;179429313 |
| N2B | 18117 | 54574;54575;54576 | chr2:178564588;178564587;178564586 | chr2:179429315;179429314;179429313 |
| Novex-1 | 18242 | 54949;54950;54951 | chr2:178564588;178564587;178564586 | chr2:179429315;179429314;179429313 |
| Novex-2 | 18309 | 55150;55151;55152 | chr2:178564588;178564587;178564586 | chr2:179429315;179429314;179429313 |
| 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/F | rs879178329  |
-1.441 | 0.991 | N | 0.574 | 0.343 | 0.530160902827 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/F | rs879178329 |
-1.441 | 0.991 | N | 0.574 | 0.343 | 0.530160902827 | gnomAD-4.0.0 | 6.84348E-07 | None | None | None | None | N | None | 0 | 2.23784E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/N | rs373448447 |
-0.62 | 0.997 | N | 0.761 | 0.511 | None | gnomAD-2.1.1 | 3.22E-05 | None | None | None | None | N | None | 3.72116E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/N | rs373448447 |
-0.62 | 0.997 | N | 0.761 | 0.511 | None | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 9.65E-05 | 1.30976E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.78011E-04 |
| I/N | rs373448447 |
-0.62 | 0.997 | N | 0.761 | 0.511 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 1.5E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| I/N | rs373448447 |
-0.62 | 0.997 | N | 0.761 | 0.511 | None | gnomAD-4.0.0 | 7.43719E-06 | None | None | None | None | N | None | 1.19974E-04 | 3.33456E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.60102E-05 |
| I/V | rs879178329 |
None | 0.02 | N | 0.159 | 0.068 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs879178329 |
None | 0.02 | N | 0.159 | 0.068 | None | gnomAD-4.0.0 | 1.23962E-06 | None | None | None | None | N | None | 1.33508E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.47683E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.7572 | likely_pathogenic | 0.7847 | pathogenic | -1.955 | Destabilizing | 0.91 | D | 0.504 | neutral | None | None | None | None | N |
| I/C | 0.8578 | likely_pathogenic | 0.8691 | pathogenic | -1.771 | Destabilizing | 0.999 | D | 0.643 | neutral | None | None | None | None | N |
| I/D | 0.9815 | likely_pathogenic | 0.9801 | pathogenic | -2.348 | Highly Destabilizing | 0.998 | D | 0.769 | deleterious | None | None | None | None | N |
| I/E | 0.9442 | likely_pathogenic | 0.9431 | pathogenic | -2.309 | Highly Destabilizing | 0.993 | D | 0.771 | deleterious | None | None | None | None | N |
| I/F | 0.522 | ambiguous | 0.4681 | ambiguous | -1.537 | Destabilizing | 0.991 | D | 0.574 | neutral | N | 0.484489971 | None | None | N |
| I/G | 0.9463 | likely_pathogenic | 0.9497 | pathogenic | -2.301 | Highly Destabilizing | 0.993 | D | 0.765 | deleterious | None | None | None | None | N |
| I/H | 0.9263 | likely_pathogenic | 0.9255 | pathogenic | -1.593 | Destabilizing | 0.999 | D | 0.734 | prob.delet. | None | None | None | None | N |
| I/K | 0.8489 | likely_pathogenic | 0.8481 | pathogenic | -1.411 | Destabilizing | 0.993 | D | 0.766 | deleterious | None | None | None | None | N |
| I/L | 0.3208 | likely_benign | 0.3275 | benign | -1.042 | Destabilizing | 0.58 | D | 0.261 | neutral | N | 0.513171769 | None | None | N |
| I/M | 0.2426 | likely_benign | 0.2494 | benign | -1.027 | Destabilizing | 0.991 | D | 0.557 | neutral | N | 0.486692017 | None | None | N |
| I/N | 0.8012 | likely_pathogenic | 0.7944 | pathogenic | -1.452 | Destabilizing | 0.997 | D | 0.761 | deleterious | N | 0.512429594 | None | None | N |
| I/P | 0.9605 | likely_pathogenic | 0.9638 | pathogenic | -1.32 | Destabilizing | 0.998 | D | 0.775 | deleterious | None | None | None | None | N |
| I/Q | 0.8894 | likely_pathogenic | 0.8981 | pathogenic | -1.655 | Destabilizing | 0.998 | D | 0.753 | deleterious | None | None | None | None | N |
| I/R | 0.8118 | likely_pathogenic | 0.8094 | pathogenic | -0.868 | Destabilizing | 0.993 | D | 0.761 | deleterious | None | None | None | None | N |
| I/S | 0.7458 | likely_pathogenic | 0.7631 | pathogenic | -2.03 | Highly Destabilizing | 0.991 | D | 0.705 | prob.neutral | N | 0.516636149 | None | None | N |
| I/T | 0.489 | ambiguous | 0.5242 | ambiguous | -1.873 | Destabilizing | 0.939 | D | 0.586 | neutral | D | 0.522407328 | None | None | N |
| I/V | 0.0804 | likely_benign | 0.0879 | benign | -1.32 | Destabilizing | 0.02 | N | 0.159 | neutral | N | 0.402019777 | None | None | N |
| I/W | 0.9633 | likely_pathogenic | 0.9559 | pathogenic | -1.679 | Destabilizing | 0.999 | D | 0.718 | prob.delet. | None | None | None | None | N |
| I/Y | 0.8877 | likely_pathogenic | 0.8677 | pathogenic | -1.397 | Destabilizing | 0.998 | D | 0.683 | 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.