Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20115 | 60568;60569;60570 | chr2:178591382;178591381;178591380 | chr2:179456109;179456108;179456107 |
| N2AB | 18474 | 55645;55646;55647 | chr2:178591382;178591381;178591380 | chr2:179456109;179456108;179456107 |
| N2A | 17547 | 52864;52865;52866 | chr2:178591382;178591381;178591380 | chr2:179456109;179456108;179456107 |
| N2B | 11050 | 33373;33374;33375 | chr2:178591382;178591381;178591380 | chr2:179456109;179456108;179456107 |
| Novex-1 | 11175 | 33748;33749;33750 | chr2:178591382;178591381;178591380 | chr2:179456109;179456108;179456107 |
| Novex-2 | 11242 | 33949;33950;33951 | chr2:178591382;178591381;178591380 | chr2:179456109;179456108;179456107 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs376618165  |
0.016 | 0.767 | N | 0.238 | 0.076 | 0.229264304666 | gnomAD-2.1.1 | 2.42E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 5.34E-05 | 0 |
| D/E | rs376618165 |
0.016 | 0.767 | N | 0.238 | 0.076 | 0.229264304666 | gnomAD-4.0.0 | 2.66927E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.41886E-05 | 0 | 1.65706E-05 |
| D/G | None | None | 0.998 | N | 0.638 | 0.418 | 0.282179105231 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| D/N | rs369893671 |
0.248 | 1.0 | N | 0.617 | 0.393 | None | gnomAD-2.1.1 | 2.5E-05 | None | None | None | None | N | None | 1.65385E-04 | 0 | None | 0 | 5.13E-05 | None | 0 | None | 0 | 1.57E-05 | 0 |
| D/N | rs369893671 |
0.248 | 1.0 | N | 0.617 | 0.393 | None | gnomAD-3.1.2 | 5.92E-05 | None | None | None | None | N | None | 1.93134E-04 | 0 | 0 | 0 | 1.94477E-04 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs369893671 |
0.248 | 1.0 | N | 0.617 | 0.393 | None | gnomAD-4.0.0 | 1.98391E-05 | None | None | None | None | N | None | 1.73667E-04 | 0 | None | 0 | 4.4615E-05 | None | 0 | 0 | 1.10223E-05 | 3.29678E-05 | 1.60174E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1059 | likely_benign | 0.1174 | benign | 0.147 | Stabilizing | 0.996 | D | 0.609 | neutral | N | 0.469600222 | None | None | N |
| D/C | 0.4006 | ambiguous | 0.4566 | ambiguous | 0.157 | Stabilizing | 1.0 | D | 0.642 | neutral | None | None | None | None | N |
| D/E | 0.1254 | likely_benign | 0.1328 | benign | -0.279 | Destabilizing | 0.767 | D | 0.238 | neutral | N | 0.48543809 | None | None | N |
| D/F | 0.4559 | ambiguous | 0.4971 | ambiguous | -0.095 | Destabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | N |
| D/G | 0.0929 | likely_benign | 0.112 | benign | 0.081 | Stabilizing | 0.998 | D | 0.638 | neutral | N | 0.45427699 | None | None | N |
| D/H | 0.2036 | likely_benign | 0.2298 | benign | 0.336 | Stabilizing | 1.0 | D | 0.627 | neutral | N | 0.498580257 | None | None | N |
| D/I | 0.3363 | likely_benign | 0.3564 | ambiguous | 0.247 | Stabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| D/K | 0.2294 | likely_benign | 0.2561 | benign | 0.603 | Stabilizing | 0.999 | D | 0.656 | neutral | None | None | None | None | N |
| D/L | 0.3065 | likely_benign | 0.3373 | benign | 0.247 | Stabilizing | 1.0 | D | 0.675 | prob.neutral | None | None | None | None | N |
| D/M | 0.4375 | ambiguous | 0.4623 | ambiguous | 0.185 | Stabilizing | 1.0 | D | 0.637 | neutral | None | None | None | None | N |
| D/N | 0.0732 | likely_benign | 0.0735 | benign | 0.499 | Stabilizing | 1.0 | D | 0.617 | neutral | N | 0.476698389 | None | None | N |
| D/P | 0.6746 | likely_pathogenic | 0.7488 | pathogenic | 0.23 | Stabilizing | 1.0 | D | 0.664 | neutral | None | None | None | None | N |
| D/Q | 0.2146 | likely_benign | 0.24 | benign | 0.483 | Stabilizing | 0.999 | D | 0.668 | neutral | None | None | None | None | N |
| D/R | 0.2546 | likely_benign | 0.2915 | benign | 0.608 | Stabilizing | 0.999 | D | 0.647 | neutral | None | None | None | None | N |
| D/S | 0.0908 | likely_benign | 0.0961 | benign | 0.422 | Stabilizing | 0.997 | D | 0.585 | neutral | None | None | None | None | N |
| D/T | 0.1812 | likely_benign | 0.1931 | benign | 0.482 | Stabilizing | 1.0 | D | 0.65 | neutral | None | None | None | None | N |
| D/V | 0.2029 | likely_benign | 0.2212 | benign | 0.23 | Stabilizing | 0.999 | D | 0.678 | prob.neutral | N | 0.477437809 | None | None | N |
| D/W | 0.7547 | likely_pathogenic | 0.7986 | pathogenic | -0.133 | Destabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | N |
| D/Y | 0.1969 | likely_benign | 0.2181 | benign | 0.105 | Stabilizing | 1.0 | D | 0.653 | neutral | N | 0.505581696 | 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.