Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21350 | 64273;64274;64275 | chr2:178587163;178587162;178587161 | chr2:179451890;179451889;179451888 |
| N2AB | 19709 | 59350;59351;59352 | chr2:178587163;178587162;178587161 | chr2:179451890;179451889;179451888 |
| N2A | 18782 | 56569;56570;56571 | chr2:178587163;178587162;178587161 | chr2:179451890;179451889;179451888 |
| N2B | 12285 | 37078;37079;37080 | chr2:178587163;178587162;178587161 | chr2:179451890;179451889;179451888 |
| Novex-1 | 12410 | 37453;37454;37455 | chr2:178587163;178587162;178587161 | chr2:179451890;179451889;179451888 |
| Novex-2 | 12477 | 37654;37655;37656 | chr2:178587163;178587162;178587161 | chr2:179451890;179451889;179451888 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/F | None | None | 0.999 | D | 0.753 | 0.284 | 0.661631946462 | gnomAD-4.0.0 | 4.79076E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.29795E-06 | 0 | 0 |
| V/I | rs772377673  |
-0.354 | 0.993 | D | 0.504 | 0.231 | 0.581883730242 | gnomAD-2.1.1 | 2.81E-05 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 5.57E-05 | None | 1.30727E-04 | None | 0 | 0 | 1.65673E-04 |
| V/I | rs772377673 |
-0.354 | 0.993 | D | 0.504 | 0.231 | 0.581883730242 | gnomAD-4.0.0 | 1.02659E-05 | None | None | None | None | N | None | 8.97559E-05 | 2.23664E-05 | None | 0 | 5.04032E-05 | None | 0 | 0 | 3.59883E-06 | 3.4785E-05 | 3.31455E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1904 | likely_benign | 0.1826 | benign | -0.993 | Destabilizing | 0.996 | D | 0.499 | neutral | N | 0.448272142 | None | None | N |
| V/C | 0.6418 | likely_pathogenic | 0.6239 | pathogenic | -0.776 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | N |
| V/D | 0.358 | ambiguous | 0.3268 | benign | -0.765 | Destabilizing | 1.0 | D | 0.821 | deleterious | N | 0.444021116 | None | None | N |
| V/E | 0.2393 | likely_benign | 0.2246 | benign | -0.868 | Destabilizing | 1.0 | D | 0.772 | deleterious | None | None | None | None | N |
| V/F | 0.177 | likely_benign | 0.1709 | benign | -1.152 | Destabilizing | 0.999 | D | 0.753 | deleterious | D | 0.524444769 | None | None | N |
| V/G | 0.2595 | likely_benign | 0.2458 | benign | -1.165 | Destabilizing | 1.0 | D | 0.776 | deleterious | N | 0.516611933 | None | None | N |
| V/H | 0.5562 | ambiguous | 0.5256 | ambiguous | -0.683 | Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | N |
| V/I | 0.0664 | likely_benign | 0.0671 | benign | -0.674 | Destabilizing | 0.993 | D | 0.504 | neutral | D | 0.524618127 | None | None | N |
| V/K | 0.3808 | ambiguous | 0.3362 | benign | -0.679 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| V/L | 0.1359 | likely_benign | 0.1247 | benign | -0.674 | Destabilizing | 0.491 | N | 0.291 | neutral | N | 0.448677574 | None | None | N |
| V/M | 0.1164 | likely_benign | 0.1181 | benign | -0.471 | Destabilizing | 0.998 | D | 0.733 | prob.delet. | None | None | None | None | N |
| V/N | 0.2229 | likely_benign | 0.2083 | benign | -0.405 | Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| V/P | 0.4375 | ambiguous | 0.4464 | ambiguous | -0.746 | Destabilizing | 1.0 | D | 0.802 | deleterious | None | None | None | None | N |
| V/Q | 0.2891 | likely_benign | 0.2635 | benign | -0.725 | Destabilizing | 1.0 | D | 0.818 | deleterious | None | None | None | None | N |
| V/R | 0.4027 | ambiguous | 0.354 | ambiguous | -0.09 | Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | N |
| V/S | 0.2124 | likely_benign | 0.1969 | benign | -0.816 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | N |
| V/T | 0.1872 | likely_benign | 0.1834 | benign | -0.825 | Destabilizing | 0.997 | D | 0.653 | neutral | None | None | None | None | N |
| V/W | 0.8229 | likely_pathogenic | 0.8159 | pathogenic | -1.18 | Destabilizing | 1.0 | D | 0.8 | deleterious | None | None | None | None | N |
| V/Y | 0.5045 | ambiguous | 0.4768 | ambiguous | -0.893 | Destabilizing | 1.0 | D | 0.77 | 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.