Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23016 | 69271;69272;69273 | chr2:178577289;178577288;178577287 | chr2:179442016;179442015;179442014 |
| N2AB | 21375 | 64348;64349;64350 | chr2:178577289;178577288;178577287 | chr2:179442016;179442015;179442014 |
| N2A | 20448 | 61567;61568;61569 | chr2:178577289;178577288;178577287 | chr2:179442016;179442015;179442014 |
| N2B | 13951 | 42076;42077;42078 | chr2:178577289;178577288;178577287 | chr2:179442016;179442015;179442014 |
| Novex-1 | 14076 | 42451;42452;42453 | chr2:178577289;178577288;178577287 | chr2:179442016;179442015;179442014 |
| Novex-2 | 14143 | 42652;42653;42654 | chr2:178577289;178577288;178577287 | chr2:179442016;179442015;179442014 |
| 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/C | rs774004059  |
None | 1.0 | D | 0.695 | 0.778 | 0.701202496522 | gnomAD-4.0.0 | 2.7376E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.52704E-05 | None | 0 | 0 | 2.69887E-06 | 0 | 0 |
| G/S | rs774004059 |
-0.789 | 1.0 | D | 0.824 | 0.776 | 0.580864329964 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.65E-05 | 0 | 0 |
| G/S | rs774004059 |
-0.789 | 1.0 | D | 0.824 | 0.776 | 0.580864329964 | gnomAD-3.1.2 | 6.6E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 9.49E-05 | 0 | 0 | 0 | 0 |
| G/S | rs774004059 |
-0.789 | 1.0 | D | 0.824 | 0.776 | 0.580864329964 | gnomAD-4.0.0 | 6.60049E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 9.49127E-05 | 0 | 0 | 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 | 0.3849 | ambiguous | 0.3316 | benign | -0.645 | Destabilizing | 1.0 | D | 0.745 | deleterious | D | 0.575862555 | None | None | I |
| G/C | 0.7109 | likely_pathogenic | 0.6896 | pathogenic | -0.832 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | D | 0.647176387 | None | None | I |
| G/D | 0.8175 | likely_pathogenic | 0.813 | pathogenic | -0.814 | Destabilizing | 1.0 | D | 0.782 | deleterious | D | 0.621234667 | None | None | I |
| G/E | 0.8747 | likely_pathogenic | 0.8699 | pathogenic | -0.873 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | I |
| G/F | 0.971 | likely_pathogenic | 0.9722 | pathogenic | -1.008 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | I |
| G/H | 0.9546 | likely_pathogenic | 0.9528 | pathogenic | -1.265 | Destabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | I |
| G/I | 0.9629 | likely_pathogenic | 0.9633 | pathogenic | -0.265 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | I |
| G/K | 0.9427 | likely_pathogenic | 0.9387 | pathogenic | -1.095 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | I |
| G/L | 0.9317 | likely_pathogenic | 0.9271 | pathogenic | -0.265 | Destabilizing | 1.0 | D | 0.712 | prob.delet. | None | None | None | None | I |
| G/M | 0.9445 | likely_pathogenic | 0.939 | pathogenic | -0.234 | Destabilizing | 1.0 | D | 0.692 | prob.neutral | None | None | None | None | I |
| G/N | 0.878 | likely_pathogenic | 0.8795 | pathogenic | -0.758 | Destabilizing | 1.0 | D | 0.822 | deleterious | None | None | None | None | I |
| G/P | 0.997 | likely_pathogenic | 0.9971 | pathogenic | -0.349 | Destabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | None | I |
| G/Q | 0.8742 | likely_pathogenic | 0.8634 | pathogenic | -0.914 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | I |
| G/R | 0.8634 | likely_pathogenic | 0.8613 | pathogenic | -0.832 | Destabilizing | 1.0 | D | 0.765 | deleterious | D | 0.646974583 | None | None | I |
| G/S | 0.3506 | ambiguous | 0.3291 | benign | -1.055 | Destabilizing | 1.0 | D | 0.824 | deleterious | D | 0.59294094 | None | None | I |
| G/T | 0.7864 | likely_pathogenic | 0.765 | pathogenic | -1.023 | Destabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | I |
| G/V | 0.9023 | likely_pathogenic | 0.8991 | pathogenic | -0.349 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | D | 0.647176387 | None | None | I |
| G/W | 0.9552 | likely_pathogenic | 0.9618 | pathogenic | -1.365 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | I |
| G/Y | 0.9629 | likely_pathogenic | 0.962 | pathogenic | -0.929 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | 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.