Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 10046 | 30361;30362;30363 | chr2:178704234;178704233;178704232 | chr2:179568961;179568960;179568959 |
| N2AB | 9729 | 29410;29411;29412 | chr2:178704234;178704233;178704232 | chr2:179568961;179568960;179568959 |
| N2A | 8802 | 26629;26630;26631 | chr2:178704234;178704233;178704232 | chr2:179568961;179568960;179568959 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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/A | rs768446273  |
-0.809 | 0.019 | None | 0.451 | 0.186 | 0.231873229951 | gnomAD-2.1.1 | 4.01E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.85E-06 | 0 |
| T/I | rs535268419 |
0.24 | None | None | 0.325 | 0.209 | None | gnomAD-2.1.1 | 2.81E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 2.28743E-04 | None | 0 | 0 | 0 |
| T/I | rs535268419 |
0.24 | None | None | 0.325 | 0.209 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.06782E-04 | 0 |
| T/I | rs535268419 |
0.24 | None | None | 0.325 | 0.209 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| T/I | rs535268419 |
0.24 | None | None | 0.325 | 0.209 | None | gnomAD-4.0.0 | 9.29383E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.64962E-04 | 0 | 1.42716E-04 | 1.60041E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1419 | likely_benign | 0.2003 | benign | -0.907 | Destabilizing | 0.019 | N | 0.451 | neutral | None | None | None | None | N |
| T/C | 0.6139 | likely_pathogenic | 0.7785 | pathogenic | -0.897 | Destabilizing | 0.667 | D | 0.566 | neutral | None | None | None | None | N |
| T/D | 0.6588 | likely_pathogenic | 0.79 | pathogenic | -1.674 | Destabilizing | 0.22 | N | 0.567 | neutral | None | None | None | None | N |
| T/E | 0.4512 | ambiguous | 0.5596 | ambiguous | -1.57 | Destabilizing | 0.124 | N | 0.553 | neutral | None | None | None | None | N |
| T/F | 0.254 | likely_benign | 0.3596 | ambiguous | -0.72 | Destabilizing | 0.22 | N | 0.578 | neutral | None | None | None | None | N |
| T/G | 0.5636 | ambiguous | 0.7192 | pathogenic | -1.248 | Destabilizing | 0.055 | N | 0.507 | neutral | None | None | None | None | N |
| T/H | 0.2768 | likely_benign | 0.3943 | ambiguous | -1.499 | Destabilizing | 0.667 | D | 0.536 | neutral | None | None | None | None | N |
| T/I | 0.1496 | likely_benign | 0.1916 | benign | -0.056 | Destabilizing | None | N | 0.325 | neutral | None | None | None | None | N |
| T/K | 0.2896 | likely_benign | 0.3867 | ambiguous | -0.906 | Destabilizing | 0.124 | N | 0.555 | neutral | None | None | None | None | N |
| T/L | 0.1375 | likely_benign | 0.1761 | benign | -0.056 | Destabilizing | None | N | 0.326 | neutral | None | None | None | None | N |
| T/M | 0.1062 | likely_benign | 0.1246 | benign | 0.108 | Stabilizing | 0.497 | N | 0.585 | neutral | None | None | None | None | N |
| T/N | 0.2122 | likely_benign | 0.3103 | benign | -1.346 | Destabilizing | 0.096 | N | 0.509 | neutral | None | None | None | None | N |
| T/P | 0.8533 | likely_pathogenic | 0.9185 | pathogenic | -0.307 | Destabilizing | 0.301 | N | 0.597 | neutral | None | None | None | None | N |
| T/Q | 0.2965 | likely_benign | 0.3731 | ambiguous | -1.374 | Destabilizing | 0.497 | N | 0.615 | neutral | None | None | None | None | N |
| T/R | 0.2146 | likely_benign | 0.2974 | benign | -0.816 | Destabilizing | 0.22 | N | 0.622 | neutral | None | None | None | None | N |
| T/S | 0.1695 | likely_benign | 0.2399 | benign | -1.459 | Destabilizing | None | N | 0.229 | neutral | None | None | None | None | N |
| T/V | 0.1552 | likely_benign | 0.1887 | benign | -0.307 | Destabilizing | 0.002 | N | 0.237 | neutral | None | None | None | None | N |
| T/W | 0.6154 | likely_pathogenic | 0.7397 | pathogenic | -0.826 | Destabilizing | 0.958 | D | 0.563 | neutral | None | None | None | None | N |
| T/Y | 0.3254 | likely_benign | 0.4658 | ambiguous | -0.492 | Destabilizing | 0.667 | D | 0.597 | neutral | 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.