Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30681 | 92266;92267;92268 | chr2:178549681;178549680;178549679 | chr2:179414408;179414407;179414406 |
| N2AB | 29040 | 87343;87344;87345 | chr2:178549681;178549680;178549679 | chr2:179414408;179414407;179414406 |
| N2A | 28113 | 84562;84563;84564 | chr2:178549681;178549680;178549679 | chr2:179414408;179414407;179414406 |
| N2B | 21616 | 65071;65072;65073 | chr2:178549681;178549680;178549679 | chr2:179414408;179414407;179414406 |
| Novex-1 | 21741 | 65446;65447;65448 | chr2:178549681;178549680;178549679 | chr2:179414408;179414407;179414406 |
| Novex-2 | 21808 | 65647;65648;65649 | chr2:178549681;178549680;178549679 | chr2:179414408;179414407;179414406 |
| 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/D | rs201400267  |
-2.142 | 0.982 | N | 0.833 | 0.267 | None | gnomAD-2.1.1 | 1.78447E-04 | None | None | None | None | N | None | 8.27E-05 | 2.83E-05 | None | 0 | 0 | None | 0 | None | 1.9984E-04 | 3.20117E-04 | 1.40371E-04 |
| A/D | rs201400267 |
-2.142 | 0.982 | N | 0.833 | 0.267 | None | gnomAD-3.1.2 | 2.43152E-04 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 1.88395E-04 | 0 | 4.70422E-04 | 0 | 0 |
| A/D | rs201400267 |
-2.142 | 0.982 | N | 0.833 | 0.267 | None | gnomAD-4.0.0 | 4.21395E-04 | None | None | None | None | N | None | 9.3453E-05 | 5.001E-05 | None | 0 | 0 | None | 1.4059E-04 | 0 | 5.45868E-04 | 0 | 2.72174E-04 |
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 | 0.5806 | likely_pathogenic | 0.6132 | pathogenic | -0.651 | Destabilizing | 0.999 | D | 0.705 | prob.neutral | None | None | None | None | N |
| A/D | 0.9675 | likely_pathogenic | 0.9794 | pathogenic | -1.703 | Destabilizing | 0.982 | D | 0.833 | deleterious | N | 0.499682397 | None | None | N |
| A/E | 0.9469 | likely_pathogenic | 0.9637 | pathogenic | -1.493 | Destabilizing | 0.986 | D | 0.783 | deleterious | None | None | None | None | N |
| A/F | 0.824 | likely_pathogenic | 0.8836 | pathogenic | -0.479 | Destabilizing | 0.993 | D | 0.831 | deleterious | None | None | None | None | N |
| A/G | 0.3761 | ambiguous | 0.4257 | ambiguous | -1.189 | Destabilizing | 0.939 | D | 0.68 | prob.neutral | N | 0.48814314 | None | None | N |
| A/H | 0.9662 | likely_pathogenic | 0.9751 | pathogenic | -1.694 | Destabilizing | 0.999 | D | 0.831 | deleterious | None | None | None | None | N |
| A/I | 0.3529 | ambiguous | 0.4747 | ambiguous | 0.611 | Stabilizing | 0.91 | D | 0.758 | deleterious | None | None | None | None | N |
| A/K | 0.9792 | likely_pathogenic | 0.986 | pathogenic | -0.893 | Destabilizing | 0.986 | D | 0.773 | deleterious | None | None | None | None | N |
| A/L | 0.4535 | ambiguous | 0.5465 | ambiguous | 0.611 | Stabilizing | 0.91 | D | 0.749 | deleterious | None | None | None | None | N |
| A/M | 0.5288 | ambiguous | 0.6468 | pathogenic | 0.394 | Stabilizing | 0.998 | D | 0.777 | deleterious | None | None | None | None | N |
| A/N | 0.8929 | likely_pathogenic | 0.9296 | pathogenic | -1.176 | Destabilizing | 0.986 | D | 0.835 | deleterious | None | None | None | None | N |
| A/P | 0.8544 | likely_pathogenic | 0.8739 | pathogenic | 0.221 | Stabilizing | 0.991 | D | 0.773 | deleterious | N | 0.465519434 | None | None | N |
| A/Q | 0.9332 | likely_pathogenic | 0.9473 | pathogenic | -0.942 | Destabilizing | 0.993 | D | 0.761 | deleterious | None | None | None | None | N |
| A/R | 0.9654 | likely_pathogenic | 0.9734 | pathogenic | -1.108 | Destabilizing | 0.993 | D | 0.771 | deleterious | None | None | None | None | N |
| A/S | 0.2461 | likely_benign | 0.2894 | benign | -1.61 | Destabilizing | 0.58 | D | 0.343 | neutral | N | 0.518268158 | None | None | N |
| A/T | 0.1697 | likely_benign | 0.2423 | benign | -1.25 | Destabilizing | 0.885 | D | 0.688 | prob.neutral | N | 0.509283315 | None | None | N |
| A/V | 0.1417 | likely_benign | 0.1972 | benign | 0.221 | Stabilizing | 0.046 | N | 0.326 | neutral | N | 0.333268981 | None | None | N |
| A/W | 0.9847 | likely_pathogenic | 0.9901 | pathogenic | -1.258 | Destabilizing | 0.999 | D | 0.811 | deleterious | None | None | None | None | N |
| A/Y | 0.9403 | likely_pathogenic | 0.9582 | pathogenic | -0.592 | Destabilizing | 0.998 | D | 0.851 | 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.