Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26439 | 79540;79541;79542 | chr2:178566817;178566816;178566815 | chr2:179431544;179431543;179431542 |
| N2AB | 24798 | 74617;74618;74619 | chr2:178566817;178566816;178566815 | chr2:179431544;179431543;179431542 |
| N2A | 23871 | 71836;71837;71838 | chr2:178566817;178566816;178566815 | chr2:179431544;179431543;179431542 |
| N2B | 17374 | 52345;52346;52347 | chr2:178566817;178566816;178566815 | chr2:179431544;179431543;179431542 |
| Novex-1 | 17499 | 52720;52721;52722 | chr2:178566817;178566816;178566815 | chr2:179431544;179431543;179431542 |
| Novex-2 | 17566 | 52921;52922;52923 | chr2:178566817;178566816;178566815 | chr2:179431544;179431543;179431542 |
| 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 | rs372968732  |
-0.342 | 1.0 | N | 0.584 | 0.376 | None | gnomAD-2.1.1 | 2.82E-05 | None | None | None | None | I | None | 6.47E-05 | 8.71E-05 | None | 0 | 0 | None | 0 | None | 0 | 2.67E-05 | 0 |
| R/C | rs372968732 |
-0.342 | 1.0 | N | 0.584 | 0.376 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/C | rs372968732 |
-0.342 | 1.0 | N | 0.584 | 0.376 | None | gnomAD-4.0.0 | 2.9755E-05 | None | None | None | None | I | None | 9.34879E-05 | 5.0045E-05 | None | 0 | 0 | None | 0 | 0 | 3.13652E-05 | 0 | 1.60159E-05 |
| R/H | rs187941835 |
-0.558 | 0.159 | N | 0.273 | 0.111 | None | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | I | None | 0 | 2.9E-05 | None | 0 | 1.11919E-04 | None | 3.27E-05 | None | 0 | 0 | 0 |
| R/H | rs187941835 |
-0.558 | 0.159 | N | 0.273 | 0.111 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/H | rs187941835 |
-0.558 | 0.159 | N | 0.273 | 0.111 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| R/H | rs187941835 |
-0.558 | 0.159 | N | 0.273 | 0.111 | None | gnomAD-4.0.0 | 3.40917E-05 | None | None | None | None | I | None | 0 | 5.00334E-05 | None | 0 | 4.46608E-05 | None | 3.13519E-05 | 0 | 3.98422E-05 | 1.09806E-05 | 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 | 0.7122 | likely_pathogenic | 0.8457 | pathogenic | 0.093 | Stabilizing | 0.559 | D | 0.515 | neutral | None | None | None | None | I |
| R/C | 0.3357 | likely_benign | 0.3503 | ambiguous | -0.245 | Destabilizing | 1.0 | D | 0.584 | neutral | N | 0.513035697 | None | None | I |
| R/D | 0.8659 | likely_pathogenic | 0.9306 | pathogenic | -0.353 | Destabilizing | 0.956 | D | 0.499 | neutral | None | None | None | None | I |
| R/E | 0.6612 | likely_pathogenic | 0.795 | pathogenic | -0.314 | Destabilizing | 0.86 | D | 0.489 | neutral | None | None | None | None | I |
| R/F | 0.8046 | likely_pathogenic | 0.8887 | pathogenic | -0.249 | Destabilizing | 0.978 | D | 0.561 | neutral | None | None | None | None | I |
| R/G | 0.4894 | ambiguous | 0.6672 | pathogenic | -0.033 | Destabilizing | 0.855 | D | 0.542 | neutral | N | 0.4573157 | None | None | I |
| R/H | 0.1723 | likely_benign | 0.2425 | benign | -0.571 | Destabilizing | 0.159 | N | 0.273 | neutral | N | 0.4843103 | None | None | I |
| R/I | 0.5875 | likely_pathogenic | 0.7237 | pathogenic | 0.379 | Stabilizing | 0.978 | D | 0.564 | neutral | None | None | None | None | I |
| R/K | 0.1241 | likely_benign | 0.1571 | benign | -0.149 | Destabilizing | 0.717 | D | 0.439 | neutral | None | None | None | None | I |
| R/L | 0.5127 | ambiguous | 0.6674 | pathogenic | 0.379 | Stabilizing | 0.922 | D | 0.505 | neutral | N | 0.492313708 | None | None | I |
| R/M | 0.5735 | likely_pathogenic | 0.7242 | pathogenic | -0.11 | Destabilizing | 0.998 | D | 0.492 | neutral | None | None | None | None | I |
| R/N | 0.7676 | likely_pathogenic | 0.8632 | pathogenic | -0.108 | Destabilizing | 0.86 | D | 0.492 | neutral | None | None | None | None | I |
| R/P | 0.9003 | likely_pathogenic | 0.9505 | pathogenic | 0.301 | Stabilizing | 0.988 | D | 0.556 | neutral | N | 0.508701738 | None | None | I |
| R/Q | 0.1584 | likely_benign | 0.2255 | benign | -0.111 | Destabilizing | 0.956 | D | 0.482 | neutral | None | None | None | None | I |
| R/S | 0.7694 | likely_pathogenic | 0.8813 | pathogenic | -0.217 | Destabilizing | 0.136 | N | 0.307 | neutral | N | 0.424085774 | None | None | I |
| R/T | 0.5598 | ambiguous | 0.7283 | pathogenic | -0.08 | Destabilizing | 0.754 | D | 0.543 | neutral | None | None | None | None | I |
| R/V | 0.6447 | likely_pathogenic | 0.7706 | pathogenic | 0.301 | Stabilizing | 0.956 | D | 0.559 | neutral | None | None | None | None | I |
| R/W | 0.334 | likely_benign | 0.4746 | ambiguous | -0.48 | Destabilizing | 0.998 | D | 0.616 | neutral | None | None | None | None | I |
| R/Y | 0.5865 | likely_pathogenic | 0.7113 | pathogenic | -0.073 | Destabilizing | 0.956 | D | 0.553 | 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.