Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23986 | 72181;72182;72183 | chr2:178574176;178574175;178574174 | chr2:179438903;179438902;179438901 |
| N2AB | 22345 | 67258;67259;67260 | chr2:178574176;178574175;178574174 | chr2:179438903;179438902;179438901 |
| N2A | 21418 | 64477;64478;64479 | chr2:178574176;178574175;178574174 | chr2:179438903;179438902;179438901 |
| N2B | 14921 | 44986;44987;44988 | chr2:178574176;178574175;178574174 | chr2:179438903;179438902;179438901 |
| Novex-1 | 15046 | 45361;45362;45363 | chr2:178574176;178574175;178574174 | chr2:179438903;179438902;179438901 |
| Novex-2 | 15113 | 45562;45563;45564 | chr2:178574176;178574175;178574174 | chr2:179438903;179438902;179438901 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/I | rs754373279  |
0.311 | 0.997 | N | 0.545 | 0.219 | 0.534620942121 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| V/I | rs754373279 |
0.311 | 0.997 | N | 0.545 | 0.219 | 0.534620942121 | gnomAD-4.0.0 | 1.16334E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 2.60236E-03 | 1.79914E-06 | 0 | 0 |
| V/L | rs754373279 |
0.309 | 0.997 | N | 0.653 | 0.315 | 0.438806408302 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| V/L | rs754373279 |
0.309 | 0.997 | N | 0.653 | 0.315 | 0.438806408302 | gnomAD-4.0.0 | 4.10592E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79914E-06 | 2.31884E-05 | 3.31389E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.622 | likely_pathogenic | 0.628 | pathogenic | -1.573 | Destabilizing | 0.999 | D | 0.634 | neutral | N | 0.481126291 | None | None | N |
| V/C | 0.9482 | likely_pathogenic | 0.9436 | pathogenic | -1.369 | Destabilizing | 1.0 | D | 0.8 | deleterious | None | None | None | None | N |
| V/D | 0.9935 | likely_pathogenic | 0.9931 | pathogenic | -1.429 | Destabilizing | 1.0 | D | 0.821 | deleterious | N | 0.509105594 | None | None | N |
| V/E | 0.9801 | likely_pathogenic | 0.9799 | pathogenic | -1.172 | Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | N |
| V/F | 0.7699 | likely_pathogenic | 0.8074 | pathogenic | -0.868 | Destabilizing | 1.0 | D | 0.77 | deleterious | N | 0.515609599 | None | None | N |
| V/G | 0.9278 | likely_pathogenic | 0.926 | pathogenic | -2.141 | Highly Destabilizing | 1.0 | D | 0.827 | deleterious | D | 0.557430878 | None | None | N |
| V/H | 0.9937 | likely_pathogenic | 0.9939 | pathogenic | -1.929 | Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| V/I | 0.0901 | likely_benign | 0.0986 | benign | 0.015 | Stabilizing | 0.997 | D | 0.545 | neutral | N | 0.512961126 | None | None | N |
| V/K | 0.9895 | likely_pathogenic | 0.9889 | pathogenic | -1.098 | Destabilizing | 1.0 | D | 0.816 | deleterious | None | None | None | None | N |
| V/L | 0.557 | ambiguous | 0.5965 | pathogenic | 0.015 | Stabilizing | 0.997 | D | 0.653 | neutral | N | 0.476253402 | None | None | N |
| V/M | 0.5874 | likely_pathogenic | 0.6253 | pathogenic | -0.286 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | N |
| V/N | 0.978 | likely_pathogenic | 0.9784 | pathogenic | -1.478 | Destabilizing | 1.0 | D | 0.868 | deleterious | None | None | None | None | N |
| V/P | 0.9879 | likely_pathogenic | 0.9857 | pathogenic | -0.487 | Destabilizing | 1.0 | D | 0.816 | deleterious | None | None | None | None | N |
| V/Q | 0.98 | likely_pathogenic | 0.9794 | pathogenic | -1.173 | Destabilizing | 1.0 | D | 0.863 | deleterious | None | None | None | None | N |
| V/R | 0.981 | likely_pathogenic | 0.9812 | pathogenic | -1.283 | Destabilizing | 1.0 | D | 0.868 | deleterious | None | None | None | None | N |
| V/S | 0.9098 | likely_pathogenic | 0.9099 | pathogenic | -2.221 | Highly Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | N |
| V/T | 0.8275 | likely_pathogenic | 0.8171 | pathogenic | -1.78 | Destabilizing | 0.999 | D | 0.601 | neutral | None | None | None | None | N |
| V/W | 0.9972 | likely_pathogenic | 0.9978 | pathogenic | -1.255 | Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| V/Y | 0.9789 | likely_pathogenic | 0.9818 | pathogenic | -0.837 | Destabilizing | 1.0 | D | 0.771 | 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.