Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26720 | 80383;80384;80385 | chr2:178565974;178565973;178565972 | chr2:179430701;179430700;179430699 |
| N2AB | 25079 | 75460;75461;75462 | chr2:178565974;178565973;178565972 | chr2:179430701;179430700;179430699 |
| N2A | 24152 | 72679;72680;72681 | chr2:178565974;178565973;178565972 | chr2:179430701;179430700;179430699 |
| N2B | 17655 | 53188;53189;53190 | chr2:178565974;178565973;178565972 | chr2:179430701;179430700;179430699 |
| Novex-1 | 17780 | 53563;53564;53565 | chr2:178565974;178565973;178565972 | chr2:179430701;179430700;179430699 |
| Novex-2 | 17847 | 53764;53765;53766 | chr2:178565974;178565973;178565972 | chr2:179430701;179430700;179430699 |
| 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/M | rs376363284  |
-1.474 | 0.983 | N | 0.653 | 0.259 | None | gnomAD-2.1.1 | 4.29E-05 | None | None | None | None | N | None | 4.13E-05 | 0 | None | 3.87372E-04 | 0 | None | 0 | None | 0 | 4.7E-05 | 1.40568E-04 |
| I/M | rs376363284 |
-1.474 | 0.983 | N | 0.653 | 0.259 | None | gnomAD-3.1.2 | 1.11779E-04 | None | None | None | None | N | None | 9.66E-05 | 0 | 0 | 2.88018E-04 | 0 | None | 0 | 0 | 1.7646E-04 | 0 | 0 |
| I/M | rs376363284 |
-1.474 | 0.983 | N | 0.653 | 0.259 | None | gnomAD-4.0.0 | 9.11071E-05 | None | None | None | None | N | None | 6.67717E-05 | 0 | None | 3.71672E-04 | 0 | None | 0 | 0 | 1.07657E-04 | 1.09789E-05 | 4.80415E-05 |
| I/T | rs879183549 |
None | 0.892 | D | 0.659 | 0.498 | None | gnomAD-4.0.0 | 1.59164E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02499E-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 | 0.7995 | likely_pathogenic | 0.8092 | pathogenic | -2.957 | Highly Destabilizing | 0.845 | D | 0.655 | neutral | None | None | None | None | N |
| I/C | 0.9514 | likely_pathogenic | 0.9557 | pathogenic | -2.39 | Highly Destabilizing | 0.999 | D | 0.763 | deleterious | None | None | None | None | N |
| I/D | 0.9995 | likely_pathogenic | 0.9993 | pathogenic | -3.664 | Highly Destabilizing | 0.996 | D | 0.893 | deleterious | None | None | None | None | N |
| I/E | 0.9975 | likely_pathogenic | 0.9972 | pathogenic | -3.339 | Highly Destabilizing | 0.987 | D | 0.89 | deleterious | None | None | None | None | N |
| I/F | 0.8125 | likely_pathogenic | 0.8381 | pathogenic | -1.74 | Destabilizing | 0.967 | D | 0.666 | neutral | D | 0.5239483 | None | None | N |
| I/G | 0.9908 | likely_pathogenic | 0.9914 | pathogenic | -3.583 | Highly Destabilizing | 0.987 | D | 0.885 | deleterious | None | None | None | None | N |
| I/H | 0.9981 | likely_pathogenic | 0.9979 | pathogenic | -3.278 | Highly Destabilizing | 0.999 | D | 0.882 | deleterious | None | None | None | None | N |
| I/K | 0.9957 | likely_pathogenic | 0.9946 | pathogenic | -2.284 | Highly Destabilizing | 0.987 | D | 0.891 | deleterious | None | None | None | None | N |
| I/L | 0.3437 | ambiguous | 0.328 | benign | -1.071 | Destabilizing | 0.426 | N | 0.343 | neutral | N | 0.464516605 | None | None | N |
| I/M | 0.4196 | ambiguous | 0.4135 | ambiguous | -1.353 | Destabilizing | 0.983 | D | 0.653 | neutral | N | 0.491600904 | None | None | N |
| I/N | 0.994 | likely_pathogenic | 0.9927 | pathogenic | -2.993 | Highly Destabilizing | 0.994 | D | 0.903 | deleterious | D | 0.52420179 | None | None | N |
| I/P | 0.9924 | likely_pathogenic | 0.9919 | pathogenic | -1.691 | Destabilizing | 0.996 | D | 0.896 | deleterious | None | None | None | None | N |
| I/Q | 0.9962 | likely_pathogenic | 0.9957 | pathogenic | -2.637 | Highly Destabilizing | 0.996 | D | 0.907 | deleterious | None | None | None | None | N |
| I/R | 0.9925 | likely_pathogenic | 0.9907 | pathogenic | -2.296 | Highly Destabilizing | 0.987 | D | 0.905 | deleterious | None | None | None | None | N |
| I/S | 0.9661 | likely_pathogenic | 0.9637 | pathogenic | -3.589 | Highly Destabilizing | 0.983 | D | 0.819 | deleterious | D | 0.52420179 | None | None | N |
| I/T | 0.6564 | likely_pathogenic | 0.6404 | pathogenic | -3.095 | Highly Destabilizing | 0.892 | D | 0.659 | neutral | D | 0.5239483 | None | None | N |
| I/V | 0.0716 | likely_benign | 0.0714 | benign | -1.691 | Destabilizing | 0.011 | N | 0.211 | neutral | N | 0.371635368 | None | None | N |
| I/W | 0.9964 | likely_pathogenic | 0.9967 | pathogenic | -2.184 | Highly Destabilizing | 0.999 | D | 0.849 | deleterious | None | None | None | None | N |
| I/Y | 0.9903 | likely_pathogenic | 0.9915 | pathogenic | -1.997 | Destabilizing | 0.987 | D | 0.749 | 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.