Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28116 | 84571;84572;84573 | chr2:178561786;178561785;178561784 | chr2:179426513;179426512;179426511 |
| N2AB | 26475 | 79648;79649;79650 | chr2:178561786;178561785;178561784 | chr2:179426513;179426512;179426511 |
| N2A | 25548 | 76867;76868;76869 | chr2:178561786;178561785;178561784 | chr2:179426513;179426512;179426511 |
| N2B | 19051 | 57376;57377;57378 | chr2:178561786;178561785;178561784 | chr2:179426513;179426512;179426511 |
| Novex-1 | 19176 | 57751;57752;57753 | chr2:178561786;178561785;178561784 | chr2:179426513;179426512;179426511 |
| Novex-2 | 19243 | 57952;57953;57954 | chr2:178561786;178561785;178561784 | chr2:179426513;179426512;179426511 |
| 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/T | rs1468127080  |
-2.815 | 0.081 | N | 0.686 | 0.317 | 0.68992488544 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| I/T | rs1468127080 |
-2.815 | 0.081 | N | 0.686 | 0.317 | 0.68992488544 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs1468127080 |
-2.815 | 0.081 | N | 0.686 | 0.317 | 0.68992488544 | gnomAD-4.0.0 | 5.57783E-06 | None | None | None | None | N | None | 1.33465E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 6.7812E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3481 | ambiguous | 0.3138 | benign | -2.28 | Highly Destabilizing | 0.055 | N | 0.629 | neutral | None | None | None | None | N |
| I/C | 0.7828 | likely_pathogenic | 0.7544 | pathogenic | -1.611 | Destabilizing | 0.859 | D | 0.775 | deleterious | None | None | None | None | N |
| I/D | 0.9849 | likely_pathogenic | 0.9768 | pathogenic | -2.585 | Highly Destabilizing | 0.667 | D | 0.809 | deleterious | None | None | None | None | N |
| I/E | 0.9714 | likely_pathogenic | 0.9609 | pathogenic | -2.303 | Highly Destabilizing | 0.364 | N | 0.785 | deleterious | None | None | None | None | N |
| I/F | 0.3415 | ambiguous | 0.3078 | benign | -1.365 | Destabilizing | 0.22 | N | 0.684 | prob.neutral | None | None | None | None | N |
| I/G | 0.9113 | likely_pathogenic | 0.8918 | pathogenic | -2.865 | Highly Destabilizing | 0.22 | N | 0.781 | deleterious | None | None | None | None | N |
| I/H | 0.9591 | likely_pathogenic | 0.941 | pathogenic | -2.414 | Highly Destabilizing | 0.958 | D | 0.821 | deleterious | None | None | None | None | N |
| I/K | 0.9692 | likely_pathogenic | 0.9572 | pathogenic | -1.804 | Destabilizing | 0.175 | N | 0.785 | deleterious | N | 0.495606014 | None | None | N |
| I/L | 0.2209 | likely_benign | 0.2187 | benign | -0.569 | Destabilizing | 0.003 | N | 0.408 | neutral | N | 0.447461279 | None | None | N |
| I/M | 0.1387 | likely_benign | 0.1349 | benign | -0.574 | Destabilizing | 0.003 | N | 0.456 | neutral | N | 0.47699478 | None | None | N |
| I/N | 0.8345 | likely_pathogenic | 0.7855 | pathogenic | -2.341 | Highly Destabilizing | 0.667 | D | 0.822 | deleterious | None | None | None | None | N |
| I/P | 0.9618 | likely_pathogenic | 0.9427 | pathogenic | -1.122 | Destabilizing | 0.859 | D | 0.81 | deleterious | None | None | None | None | N |
| I/Q | 0.9568 | likely_pathogenic | 0.9411 | pathogenic | -2.063 | Highly Destabilizing | 0.497 | N | 0.822 | deleterious | None | None | None | None | N |
| I/R | 0.9468 | likely_pathogenic | 0.9227 | pathogenic | -1.763 | Destabilizing | 0.427 | N | 0.824 | deleterious | N | 0.506962319 | None | None | N |
| I/S | 0.6457 | likely_pathogenic | 0.5984 | pathogenic | -3.027 | Highly Destabilizing | 0.22 | N | 0.755 | deleterious | None | None | None | None | N |
| I/T | 0.348 | ambiguous | 0.3193 | benign | -2.572 | Highly Destabilizing | 0.081 | N | 0.686 | prob.neutral | N | 0.474779507 | None | None | N |
| I/V | 0.0705 | likely_benign | 0.0686 | benign | -1.122 | Destabilizing | None | N | 0.185 | neutral | N | 0.348491937 | None | None | N |
| I/W | 0.9686 | likely_pathogenic | 0.956 | pathogenic | -1.752 | Destabilizing | 0.958 | D | 0.813 | deleterious | None | None | None | None | N |
| I/Y | 0.874 | likely_pathogenic | 0.8317 | pathogenic | -1.414 | Destabilizing | 0.667 | D | 0.795 | 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.