Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18572 | 55939;55940;55941 | chr2:178601283;178601282;178601281 | chr2:179466010;179466009;179466008 |
| N2AB | 16931 | 51016;51017;51018 | chr2:178601283;178601282;178601281 | chr2:179466010;179466009;179466008 |
| N2A | 16004 | 48235;48236;48237 | chr2:178601283;178601282;178601281 | chr2:179466010;179466009;179466008 |
| N2B | 9507 | 28744;28745;28746 | chr2:178601283;178601282;178601281 | chr2:179466010;179466009;179466008 |
| Novex-1 | 9632 | 29119;29120;29121 | chr2:178601283;178601282;178601281 | chr2:179466010;179466009;179466008 |
| Novex-2 | 9699 | 29320;29321;29322 | chr2:178601283;178601282;178601281 | chr2:179466010;179466009;179466008 |
| 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 | rs537445357  |
-0.942 | 0.435 | N | 0.428 | 0.129 | None | gnomAD-2.1.1 | 1.66E-05 | None | None | None | None | N | None | 1.69693E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/A | rs537445357 |
-0.942 | 0.435 | N | 0.428 | 0.129 | None | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 1.6887E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/A | rs537445357 |
-0.942 | 0.435 | N | 0.428 | 0.129 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| T/A | rs537445357 |
-0.942 | 0.435 | N | 0.428 | 0.129 | None | gnomAD-4.0.0 | 1.02665E-05 | None | None | None | None | N | None | 2.06521E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 8.65212E-07 | 0 | 0 |
| T/I | None | None | 0.93 | N | 0.563 | 0.104 | 0.361958692863 | gnomAD-4.0.0 | 4.26862E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.59772E-06 | 0 | 1.72939E-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 | 0.0982 | likely_benign | 0.0812 | benign | -0.868 | Destabilizing | 0.435 | N | 0.428 | neutral | N | 0.498077392 | None | None | N |
| T/C | 0.4664 | ambiguous | 0.4242 | ambiguous | -0.578 | Destabilizing | 0.995 | D | 0.496 | neutral | None | None | None | None | N |
| T/D | 0.5941 | likely_pathogenic | 0.5413 | ambiguous | -0.562 | Destabilizing | 0.712 | D | 0.61 | neutral | None | None | None | None | N |
| T/E | 0.3818 | ambiguous | 0.3284 | benign | -0.545 | Destabilizing | 0.338 | N | 0.565 | neutral | None | None | None | None | N |
| T/F | 0.3096 | likely_benign | 0.253 | benign | -0.823 | Destabilizing | 0.946 | D | 0.635 | neutral | None | None | None | None | N |
| T/G | 0.3933 | ambiguous | 0.36 | ambiguous | -1.151 | Destabilizing | 0.712 | D | 0.619 | neutral | None | None | None | None | N |
| T/H | 0.3344 | likely_benign | 0.2817 | benign | -1.428 | Destabilizing | 0.018 | N | 0.411 | neutral | None | None | None | None | N |
| T/I | 0.1354 | likely_benign | 0.1104 | benign | -0.199 | Destabilizing | 0.93 | D | 0.563 | neutral | N | 0.483532014 | None | None | N |
| T/K | 0.232 | likely_benign | 0.1804 | benign | -0.878 | Destabilizing | 0.003 | N | 0.187 | neutral | None | None | None | None | N |
| T/L | 0.0971 | likely_benign | 0.0873 | benign | -0.199 | Destabilizing | 0.712 | D | 0.61 | neutral | None | None | None | None | N |
| T/M | 0.1031 | likely_benign | 0.0869 | benign | 0.109 | Stabilizing | 0.982 | D | 0.509 | neutral | None | None | None | None | N |
| T/N | 0.2042 | likely_benign | 0.1873 | benign | -0.856 | Destabilizing | 0.651 | D | 0.537 | neutral | N | 0.508112225 | None | None | N |
| T/P | 0.2043 | likely_benign | 0.2155 | benign | -0.39 | Destabilizing | 0.93 | D | 0.561 | neutral | N | 0.484892635 | None | None | N |
| T/Q | 0.256 | likely_benign | 0.2167 | benign | -1.021 | Destabilizing | 0.712 | D | 0.587 | neutral | None | None | None | None | N |
| T/R | 0.2215 | likely_benign | 0.1467 | benign | -0.645 | Destabilizing | 0.003 | N | 0.211 | neutral | None | None | None | None | N |
| T/S | 0.1712 | likely_benign | 0.1552 | benign | -1.109 | Destabilizing | 0.435 | N | 0.488 | neutral | N | 0.518356664 | None | None | N |
| T/V | 0.0966 | likely_benign | 0.0896 | benign | -0.39 | Destabilizing | 0.834 | D | 0.524 | neutral | None | None | None | None | N |
| T/W | 0.654 | likely_pathogenic | 0.5773 | pathogenic | -0.76 | Destabilizing | 0.995 | D | 0.629 | neutral | None | None | None | None | N |
| T/Y | 0.328 | likely_benign | 0.3033 | benign | -0.537 | Destabilizing | 0.897 | D | 0.626 | 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.