Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31583 | 94972;94973;94974 | chr2:178546681;178546680;178546679 | chr2:179411408;179411407;179411406 |
| N2AB | 29942 | 90049;90050;90051 | chr2:178546681;178546680;178546679 | chr2:179411408;179411407;179411406 |
| N2A | 29015 | 87268;87269;87270 | chr2:178546681;178546680;178546679 | chr2:179411408;179411407;179411406 |
| N2B | 22518 | 67777;67778;67779 | chr2:178546681;178546680;178546679 | chr2:179411408;179411407;179411406 |
| Novex-1 | 22643 | 68152;68153;68154 | chr2:178546681;178546680;178546679 | chr2:179411408;179411407;179411406 |
| Novex-2 | 22710 | 68353;68354;68355 | chr2:178546681;178546680;178546679 | chr2:179411408;179411407;179411406 |
| 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/C | rs994448356  |
None | 1.0 | D | 0.743 | 0.48 | 0.831251610344 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/C | rs994448356 |
None | 1.0 | D | 0.743 | 0.48 | 0.831251610344 | gnomAD-4.0.0 | 3.04499E-06 | None | None | None | None | I | None | 1.7477E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.40984E-06 | 0 | 0 |
| R/H | rs727503544 |
-2.675 | 0.783 | D | 0.48 | 0.46 | 0.357929162469 | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.58E-05 | None | 3.27E-05 | None | 0 | 2.67E-05 | 0 |
| R/H | rs727503544 |
-2.675 | 0.783 | D | 0.48 | 0.46 | 0.357929162469 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/H | rs727503544 |
-2.675 | 0.783 | D | 0.48 | 0.46 | 0.357929162469 | gnomAD-4.0.0 | 1.98308E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.22836E-05 | None | 0 | 0 | 2.2886E-05 | 3.29381E-05 | 1.60118E-05 |
| R/L | rs727503544 |
None | 0.999 | N | 0.691 | 0.484 | 0.779448236879 | gnomAD-4.0.0 | 6.84236E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99501E-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 | 0.9831 | likely_pathogenic | 0.9806 | pathogenic | -2.106 | Highly Destabilizing | 0.996 | D | 0.639 | neutral | None | None | None | None | I |
| R/C | 0.6157 | likely_pathogenic | 0.6156 | pathogenic | -2.056 | Highly Destabilizing | 1.0 | D | 0.743 | deleterious | D | 0.526587511 | None | None | I |
| R/D | 0.9977 | likely_pathogenic | 0.9975 | pathogenic | -0.84 | Destabilizing | 0.999 | D | 0.708 | prob.delet. | None | None | None | None | I |
| R/E | 0.971 | likely_pathogenic | 0.9644 | pathogenic | -0.651 | Destabilizing | 0.992 | D | 0.622 | neutral | None | None | None | None | I |
| R/F | 0.9842 | likely_pathogenic | 0.9839 | pathogenic | -1.561 | Destabilizing | 0.999 | D | 0.773 | deleterious | None | None | None | None | I |
| R/G | 0.9815 | likely_pathogenic | 0.979 | pathogenic | -2.426 | Highly Destabilizing | 0.998 | D | 0.689 | prob.neutral | D | 0.562542532 | None | None | I |
| R/H | 0.3328 | likely_benign | 0.3365 | benign | -2.275 | Highly Destabilizing | 0.783 | D | 0.48 | neutral | D | 0.533170877 | None | None | I |
| R/I | 0.9649 | likely_pathogenic | 0.959 | pathogenic | -1.187 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | I |
| R/K | 0.5587 | ambiguous | 0.4846 | ambiguous | -1.531 | Destabilizing | 0.99 | D | 0.682 | prob.neutral | None | None | None | None | I |
| R/L | 0.9203 | likely_pathogenic | 0.918 | pathogenic | -1.187 | Destabilizing | 0.999 | D | 0.691 | prob.neutral | N | 0.521814571 | None | None | I |
| R/M | 0.9697 | likely_pathogenic | 0.9622 | pathogenic | -1.596 | Destabilizing | 1.0 | D | 0.676 | prob.neutral | None | None | None | None | I |
| R/N | 0.9883 | likely_pathogenic | 0.9869 | pathogenic | -1.264 | Destabilizing | 0.992 | D | 0.617 | neutral | None | None | None | None | I |
| R/P | 0.9995 | likely_pathogenic | 0.9994 | pathogenic | -1.482 | Destabilizing | 1.0 | D | 0.759 | deleterious | D | 0.563049511 | None | None | I |
| R/Q | 0.4471 | ambiguous | 0.4028 | ambiguous | -1.294 | Destabilizing | 0.999 | D | 0.631 | neutral | None | None | None | None | I |
| R/S | 0.9844 | likely_pathogenic | 0.9805 | pathogenic | -2.277 | Highly Destabilizing | 0.998 | D | 0.653 | neutral | N | 0.516949045 | None | None | I |
| R/T | 0.9773 | likely_pathogenic | 0.9701 | pathogenic | -1.886 | Destabilizing | 1.0 | D | 0.643 | neutral | None | None | None | None | I |
| R/V | 0.966 | likely_pathogenic | 0.961 | pathogenic | -1.482 | Destabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | None | I |
| R/W | 0.7908 | likely_pathogenic | 0.794 | pathogenic | -1.015 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | I |
| R/Y | 0.9332 | likely_pathogenic | 0.9375 | pathogenic | -0.858 | Destabilizing | 0.998 | D | 0.75 | deleterious | 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.