Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22799 | 68620;68621;68622 | chr2:178578120;178578119;178578118 | chr2:179442847;179442846;179442845 |
| N2AB | 21158 | 63697;63698;63699 | chr2:178578120;178578119;178578118 | chr2:179442847;179442846;179442845 |
| N2A | 20231 | 60916;60917;60918 | chr2:178578120;178578119;178578118 | chr2:179442847;179442846;179442845 |
| N2B | 13734 | 41425;41426;41427 | chr2:178578120;178578119;178578118 | chr2:179442847;179442846;179442845 |
| Novex-1 | 13859 | 41800;41801;41802 | chr2:178578120;178578119;178578118 | chr2:179442847;179442846;179442845 |
| Novex-2 | 13926 | 42001;42002;42003 | chr2:178578120;178578119;178578118 | chr2:179442847;179442846;179442845 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/M | rs760928333  |
-0.036 | 1.0 | N | 0.745 | 0.331 | 0.469907520169 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| R/M | rs760928333 |
-0.036 | 1.0 | N | 0.745 | 0.331 | 0.469907520169 | gnomAD-4.0.0 | 6.84436E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99706E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.4194 | ambiguous | 0.4237 | ambiguous | 0.1 | Stabilizing | 0.999 | D | 0.629 | neutral | None | None | None | None | I |
| R/C | 0.2125 | likely_benign | 0.2407 | benign | -0.146 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | I |
| R/D | 0.7067 | likely_pathogenic | 0.7365 | pathogenic | -0.182 | Destabilizing | 1.0 | D | 0.686 | prob.neutral | None | None | None | None | I |
| R/E | 0.4728 | ambiguous | 0.4618 | ambiguous | -0.13 | Destabilizing | 0.999 | D | 0.667 | neutral | None | None | None | None | I |
| R/F | 0.5881 | likely_pathogenic | 0.5868 | pathogenic | -0.177 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | I |
| R/G | 0.2769 | likely_benign | 0.2902 | benign | -0.063 | Destabilizing | 1.0 | D | 0.606 | neutral | N | 0.460953438 | None | None | I |
| R/H | 0.1208 | likely_benign | 0.1309 | benign | -0.576 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | I |
| R/I | 0.3663 | ambiguous | 0.3734 | ambiguous | 0.486 | Stabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | I |
| R/K | 0.11 | likely_benign | 0.0998 | benign | -0.042 | Destabilizing | 0.997 | D | 0.55 | neutral | N | 0.411716696 | None | None | I |
| R/L | 0.2808 | likely_benign | 0.2949 | benign | 0.486 | Stabilizing | 1.0 | D | 0.606 | neutral | None | None | None | None | I |
| R/M | 0.3492 | ambiguous | 0.3519 | ambiguous | 0.009 | Stabilizing | 1.0 | D | 0.745 | deleterious | N | 0.49981847 | None | None | I |
| R/N | 0.6041 | likely_pathogenic | 0.6278 | pathogenic | 0.084 | Stabilizing | 1.0 | D | 0.738 | prob.delet. | None | None | None | None | I |
| R/P | 0.3647 | ambiguous | 0.4078 | ambiguous | 0.377 | Stabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | I |
| R/Q | 0.1185 | likely_benign | 0.1272 | benign | 0.036 | Stabilizing | 1.0 | D | 0.732 | prob.delet. | None | None | None | None | I |
| R/S | 0.4974 | ambiguous | 0.5241 | ambiguous | -0.137 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | N | 0.406598878 | None | None | I |
| R/T | 0.2824 | likely_benign | 0.303 | benign | 0.032 | Stabilizing | 1.0 | D | 0.679 | prob.neutral | N | 0.410924475 | None | None | I |
| R/V | 0.4033 | ambiguous | 0.4108 | ambiguous | 0.377 | Stabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | I |
| R/W | 0.2194 | likely_benign | 0.2424 | benign | -0.328 | Destabilizing | 1.0 | D | 0.757 | deleterious | N | 0.48035846 | None | None | I |
| R/Y | 0.4374 | ambiguous | 0.4601 | ambiguous | 0.088 | Stabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | I |
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.