Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33400 | 100423;100424;100425 | chr2:178536549;178536548;178536547 | chr2:179401276;179401275;179401274 |
| N2AB | 31759 | 95500;95501;95502 | chr2:178536549;178536548;178536547 | chr2:179401276;179401275;179401274 |
| N2A | 30832 | 92719;92720;92721 | chr2:178536549;178536548;178536547 | chr2:179401276;179401275;179401274 |
| N2B | 24335 | 73228;73229;73230 | chr2:178536549;178536548;178536547 | chr2:179401276;179401275;179401274 |
| Novex-1 | 24460 | 73603;73604;73605 | chr2:178536549;178536548;178536547 | chr2:179401276;179401275;179401274 |
| Novex-2 | 24527 | 73804;73805;73806 | chr2:178536549;178536548;178536547 | chr2:179401276;179401275;179401274 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs1034663911  |
None | 0.001 | N | 0.225 | 0.099 | 0.231231049324 | gnomAD-4.0.0 | 7.37633E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.78936E-05 |
| T/S | rs1034663911 |
-0.67 | 0.005 | N | 0.153 | 0.089 | 0.107399877778 | gnomAD-2.1.1 | 5.91E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.18E-05 | 0 |
| T/S | rs1034663911 |
-0.67 | 0.005 | N | 0.153 | 0.089 | 0.107399877778 | 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 |
| T/S | rs1034663911 |
-0.67 | 0.005 | N | 0.153 | 0.089 | 0.107399877778 | gnomAD-4.0.0 | 1.32635E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.76494E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0768 | likely_benign | 0.0685 | benign | -0.718 | Destabilizing | 0.08 | N | 0.279 | neutral | N | 0.484697089 | None | None | I |
| T/C | 0.3397 | likely_benign | 0.2648 | benign | -0.487 | Destabilizing | 0.965 | D | 0.513 | neutral | None | None | None | None | I |
| T/D | 0.3277 | likely_benign | 0.3142 | benign | 0.03 | Stabilizing | 0.561 | D | 0.463 | neutral | None | None | None | None | I |
| T/E | 0.2153 | likely_benign | 0.2174 | benign | 0.04 | Stabilizing | 0.561 | D | 0.461 | neutral | None | None | None | None | I |
| T/F | 0.1682 | likely_benign | 0.1472 | benign | -0.76 | Destabilizing | 0.002 | N | 0.32 | neutral | None | None | None | None | I |
| T/G | 0.257 | likely_benign | 0.2092 | benign | -0.982 | Destabilizing | 0.209 | N | 0.409 | neutral | None | None | None | None | I |
| T/H | 0.23 | likely_benign | 0.2082 | benign | -1.26 | Destabilizing | 0.965 | D | 0.535 | neutral | None | None | None | None | I |
| T/I | 0.0953 | likely_benign | 0.0796 | benign | -0.106 | Destabilizing | 0.001 | N | 0.225 | neutral | N | 0.466631403 | None | None | I |
| T/K | 0.195 | likely_benign | 0.2113 | benign | -0.646 | Destabilizing | 0.561 | D | 0.456 | neutral | None | None | None | None | I |
| T/L | 0.085 | likely_benign | 0.0742 | benign | -0.106 | Destabilizing | 0.002 | N | 0.198 | neutral | None | None | None | None | I |
| T/M | 0.09 | likely_benign | 0.0767 | benign | 0.021 | Stabilizing | 0.818 | D | 0.55 | neutral | None | None | None | None | I |
| T/N | 0.1151 | likely_benign | 0.0959 | benign | -0.608 | Destabilizing | 0.491 | N | 0.393 | neutral | N | 0.499511826 | None | None | I |
| T/P | 0.5051 | ambiguous | 0.5709 | pathogenic | -0.277 | Destabilizing | 0.662 | D | 0.583 | neutral | N | 0.487096864 | None | None | I |
| T/Q | 0.1847 | likely_benign | 0.1823 | benign | -0.711 | Destabilizing | 0.818 | D | 0.587 | neutral | None | None | None | None | I |
| T/R | 0.1624 | likely_benign | 0.1861 | benign | -0.493 | Destabilizing | 0.561 | D | 0.601 | neutral | None | None | None | None | I |
| T/S | 0.1098 | likely_benign | 0.0909 | benign | -0.895 | Destabilizing | 0.005 | N | 0.153 | neutral | N | 0.465396465 | None | None | I |
| T/V | 0.0832 | likely_benign | 0.0692 | benign | -0.277 | Destabilizing | 0.001 | N | 0.092 | neutral | None | None | None | None | I |
| T/W | 0.5591 | ambiguous | 0.5653 | pathogenic | -0.718 | Destabilizing | 0.991 | D | 0.526 | neutral | None | None | None | None | I |
| T/Y | 0.2168 | likely_benign | 0.2067 | benign | -0.47 | Destabilizing | 0.39 | N | 0.522 | neutral | 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.