Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 7267 | 22024;22025;22026 | chr2:178723208;178723207;178723206 | chr2:179587935;179587934;179587933 |
| N2AB | 6950 | 21073;21074;21075 | chr2:178723208;178723207;178723206 | chr2:179587935;179587934;179587933 |
| N2A | 6023 | 18292;18293;18294 | chr2:178723208;178723207;178723206 | chr2:179587935;179587934;179587933 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/D | rs375627540  |
-0.544 | 0.071 | N | 0.299 | 0.3 | 0.17258766438 | gnomAD-2.1.1 | 6.15821E-04 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 5.55882E-03 | None | 0 | 7.85E-06 | 1.40964E-04 |
| G/D | rs375627540 |
-0.544 | 0.071 | N | 0.299 | 0.3 | 0.17258766438 | gnomAD-3.1.2 | 2.6304E-04 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 7.66363E-03 | 0 |
| G/D | rs375627540 |
-0.544 | 0.071 | N | 0.299 | 0.3 | 0.17258766438 | 1000 genomes | 1.99681E-03 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1.02E-02 | None |
| G/D | rs375627540 |
-0.544 | 0.071 | N | 0.299 | 0.3 | 0.17258766438 | gnomAD-4.0.0 | 3.51419E-04 | None | None | None | None | N | None | 2.66667E-05 | 0 | None | 0 | 0 | None | 0 | 1.65125E-04 | 5.93406E-06 | 5.84204E-03 | 4.00218E-04 |
| G/S | rs772450876 |
-0.839 | 0.961 | N | 0.377 | 0.395 | 0.223146558224 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.58E-05 | None | 0 | None | 0 | 0 | 0 |
| G/S | rs772450876 |
-0.839 | 0.961 | N | 0.377 | 0.395 | 0.223146558224 | gnomAD-4.0.0 | 3.1841E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.55185E-05 | None | 0 | 0 | 0 | 0 | 0 |
| G/V | None | None | 0.994 | D | 0.561 | 0.418 | 0.707368253468 | gnomAD-4.0.0 | 6.84334E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99569E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | 0.1914 | likely_benign | 0.2039 | benign | -0.35 | Destabilizing | 0.98 | D | 0.377 | neutral | N | 0.513360512 | None | None | N |
| G/C | 0.2872 | likely_benign | 0.3045 | benign | -0.904 | Destabilizing | 1.0 | D | 0.605 | neutral | D | 0.532478725 | None | None | N |
| G/D | 0.1487 | likely_benign | 0.1638 | benign | -0.474 | Destabilizing | 0.071 | N | 0.299 | neutral | N | 0.48497268 | None | None | N |
| G/E | 0.2106 | likely_benign | 0.2339 | benign | -0.627 | Destabilizing | 0.942 | D | 0.433 | neutral | None | None | None | None | N |
| G/F | 0.6324 | likely_pathogenic | 0.6715 | pathogenic | -0.986 | Destabilizing | 0.999 | D | 0.575 | neutral | None | None | None | None | N |
| G/H | 0.3295 | likely_benign | 0.3506 | ambiguous | -0.513 | Destabilizing | 0.999 | D | 0.485 | neutral | None | None | None | None | N |
| G/I | 0.3381 | likely_benign | 0.3804 | ambiguous | -0.451 | Destabilizing | 0.999 | D | 0.578 | neutral | None | None | None | None | N |
| G/K | 0.358 | ambiguous | 0.3738 | ambiguous | -0.831 | Destabilizing | 0.942 | D | 0.428 | neutral | None | None | None | None | N |
| G/L | 0.5231 | ambiguous | 0.5652 | pathogenic | -0.451 | Destabilizing | 0.996 | D | 0.567 | neutral | None | None | None | None | N |
| G/M | 0.5519 | ambiguous | 0.5951 | pathogenic | -0.54 | Destabilizing | 1.0 | D | 0.581 | neutral | None | None | None | None | N |
| G/N | 0.186 | likely_benign | 0.2036 | benign | -0.491 | Destabilizing | 0.503 | D | 0.282 | neutral | None | None | None | None | N |
| G/P | 0.922 | likely_pathogenic | 0.9319 | pathogenic | -0.384 | Destabilizing | 0.999 | D | 0.477 | neutral | None | None | None | None | N |
| G/Q | 0.28 | likely_benign | 0.2973 | benign | -0.759 | Destabilizing | 0.991 | D | 0.471 | neutral | None | None | None | None | N |
| G/R | 0.2356 | likely_benign | 0.2507 | benign | -0.373 | Destabilizing | 0.151 | N | 0.362 | neutral | N | 0.513107022 | None | None | N |
| G/S | 0.1043 | likely_benign | 0.1165 | benign | -0.672 | Destabilizing | 0.961 | D | 0.377 | neutral | N | 0.509370812 | None | None | N |
| G/T | 0.2268 | likely_benign | 0.2467 | benign | -0.749 | Destabilizing | 0.991 | D | 0.435 | neutral | None | None | None | None | N |
| G/V | 0.2963 | likely_benign | 0.338 | benign | -0.384 | Destabilizing | 0.994 | D | 0.561 | neutral | D | 0.532478725 | None | None | N |
| G/W | 0.4952 | ambiguous | 0.5183 | ambiguous | -1.134 | Destabilizing | 1.0 | D | 0.538 | neutral | None | None | None | None | N |
| G/Y | 0.4315 | ambiguous | 0.4811 | ambiguous | -0.794 | Destabilizing | 0.999 | D | 0.575 | 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.