Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28333 | 85222;85223;85224 | chr2:178561135;178561134;178561133 | chr2:179425862;179425861;179425860 |
| N2AB | 26692 | 80299;80300;80301 | chr2:178561135;178561134;178561133 | chr2:179425862;179425861;179425860 |
| N2A | 25765 | 77518;77519;77520 | chr2:178561135;178561134;178561133 | chr2:179425862;179425861;179425860 |
| N2B | 19268 | 58027;58028;58029 | chr2:178561135;178561134;178561133 | chr2:179425862;179425861;179425860 |
| Novex-1 | 19393 | 58402;58403;58404 | chr2:178561135;178561134;178561133 | chr2:179425862;179425861;179425860 |
| Novex-2 | 19460 | 58603;58604;58605 | chr2:178561135;178561134;178561133 | chr2:179425862;179425861;179425860 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/T | None | None | 1.0 | N | 0.761 | 0.396 | 0.423836183345 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 1.9305E-04 | None | 0 | 0 | 0 | 0 | 0 |
| A/T | None | None | 1.0 | N | 0.761 | 0.396 | 0.423836183345 | gnomAD-4.0.0 | 6.57419E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.9305E-04 | None | 0 | 0 | 0 | 0 | 0 |
| A/V | rs886042586  |
-0.055 | 1.0 | N | 0.709 | 0.353 | 0.42324137094 | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.35E-05 | 0 |
| A/V | rs886042586 |
-0.055 | 1.0 | N | 0.709 | 0.353 | 0.42324137094 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| A/V | rs886042586 |
-0.055 | 1.0 | N | 0.709 | 0.353 | 0.42324137094 | gnomAD-4.0.0 | 6.19718E-06 | None | None | None | None | I | None | 1.33497E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 7.62839E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.624 | likely_pathogenic | 0.6126 | pathogenic | -0.768 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | I |
| A/D | 0.7768 | likely_pathogenic | 0.7717 | pathogenic | -0.587 | Destabilizing | 1.0 | D | 0.857 | deleterious | N | 0.482168885 | None | None | I |
| A/E | 0.7434 | likely_pathogenic | 0.7394 | pathogenic | -0.753 | Destabilizing | 1.0 | D | 0.79 | deleterious | None | None | None | None | I |
| A/F | 0.5353 | ambiguous | 0.527 | ambiguous | -0.98 | Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | I |
| A/G | 0.2815 | likely_benign | 0.2557 | benign | -0.242 | Destabilizing | 1.0 | D | 0.605 | neutral | N | 0.499005693 | None | None | I |
| A/H | 0.8268 | likely_pathogenic | 0.8181 | pathogenic | -0.235 | Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | I |
| A/I | 0.4279 | ambiguous | 0.421 | ambiguous | -0.428 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | I |
| A/K | 0.8699 | likely_pathogenic | 0.8666 | pathogenic | -0.46 | Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | I |
| A/L | 0.3032 | likely_benign | 0.3147 | benign | -0.428 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | I |
| A/M | 0.3951 | ambiguous | 0.3819 | ambiguous | -0.377 | Destabilizing | 1.0 | D | 0.814 | deleterious | None | None | None | None | I |
| A/N | 0.5975 | likely_pathogenic | 0.59 | pathogenic | -0.22 | Destabilizing | 1.0 | D | 0.87 | deleterious | None | None | None | None | I |
| A/P | 0.8582 | likely_pathogenic | 0.889 | pathogenic | -0.337 | Destabilizing | 1.0 | D | 0.807 | deleterious | D | 0.539901918 | None | None | I |
| A/Q | 0.7076 | likely_pathogenic | 0.6933 | pathogenic | -0.537 | Destabilizing | 1.0 | D | 0.818 | deleterious | None | None | None | None | I |
| A/R | 0.7501 | likely_pathogenic | 0.7458 | pathogenic | 0.027 | Stabilizing | 1.0 | D | 0.816 | deleterious | None | None | None | None | I |
| A/S | 0.1419 | likely_benign | 0.1311 | benign | -0.379 | Destabilizing | 1.0 | D | 0.608 | neutral | N | 0.494285659 | None | None | I |
| A/T | 0.1962 | likely_benign | 0.178 | benign | -0.474 | Destabilizing | 1.0 | D | 0.761 | deleterious | N | 0.50465446 | None | None | I |
| A/V | 0.1987 | likely_benign | 0.1902 | benign | -0.337 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | N | 0.483771582 | None | None | I |
| A/W | 0.9093 | likely_pathogenic | 0.9128 | pathogenic | -1.07 | Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | I |
| A/Y | 0.7675 | likely_pathogenic | 0.7707 | pathogenic | -0.732 | Destabilizing | 1.0 | D | 0.876 | deleterious | 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.