Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20880 | 62863;62864;62865 | chr2:178589087;178589086;178589085 | chr2:179453814;179453813;179453812 |
| N2AB | 19239 | 57940;57941;57942 | chr2:178589087;178589086;178589085 | chr2:179453814;179453813;179453812 |
| N2A | 18312 | 55159;55160;55161 | chr2:178589087;178589086;178589085 | chr2:179453814;179453813;179453812 |
| N2B | 11815 | 35668;35669;35670 | chr2:178589087;178589086;178589085 | chr2:179453814;179453813;179453812 |
| Novex-1 | 11940 | 36043;36044;36045 | chr2:178589087;178589086;178589085 | chr2:179453814;179453813;179453812 |
| Novex-2 | 12007 | 36244;36245;36246 | chr2:178589087;178589086;178589085 | chr2:179453814;179453813;179453812 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/K | None | None | 0.122 | N | 0.136 | 0.199 | 0.194818534648 | gnomAD-4.0.0 | 1.60055E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 2.41196E-04 | 0 | 0 | 0 |
| R/S | rs1181982003  |
-1.329 | 0.961 | N | 0.569 | 0.239 | 0.16115917748 | gnomAD-2.1.1 | 4.07E-06 | None | None | None | None | N | None | 0 | 2.91E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/S | rs1181982003 |
-1.329 | 0.961 | N | 0.569 | 0.239 | 0.16115917748 | gnomAD-4.0.0 | 2.05779E-06 | None | None | None | None | N | None | 0 | 4.47708E-05 | None | 0 | 0 | None | 0 | 0 | 8.99586E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.6675 | likely_pathogenic | 0.587 | pathogenic | -1.172 | Destabilizing | 0.931 | D | 0.555 | neutral | None | None | None | None | N |
| R/C | 0.1977 | likely_benign | 0.198 | benign | -1.255 | Destabilizing | 1.0 | D | 0.714 | prob.delet. | None | None | None | None | N |
| R/D | 0.8701 | likely_pathogenic | 0.8293 | pathogenic | -0.831 | Destabilizing | 0.996 | D | 0.645 | neutral | None | None | None | None | N |
| R/E | 0.6237 | likely_pathogenic | 0.5738 | pathogenic | -0.776 | Destabilizing | 0.97 | D | 0.525 | neutral | None | None | None | None | N |
| R/F | 0.7027 | likely_pathogenic | 0.6513 | pathogenic | -1.535 | Destabilizing | 0.999 | D | 0.696 | prob.neutral | None | None | None | None | N |
| R/G | 0.4485 | ambiguous | 0.3659 | ambiguous | -1.379 | Destabilizing | 0.98 | D | 0.601 | neutral | N | 0.459451928 | None | None | N |
| R/H | 0.0974 | likely_benign | 0.0992 | benign | -1.435 | Destabilizing | 0.999 | D | 0.537 | neutral | None | None | None | None | N |
| R/I | 0.4786 | ambiguous | 0.4385 | ambiguous | -0.632 | Destabilizing | 0.999 | D | 0.701 | prob.neutral | None | None | None | None | N |
| R/K | 0.1136 | likely_benign | 0.1056 | benign | -1.328 | Destabilizing | 0.122 | N | 0.136 | neutral | N | 0.439364657 | None | None | N |
| R/L | 0.4734 | ambiguous | 0.43 | ambiguous | -0.632 | Destabilizing | 0.985 | D | 0.601 | neutral | None | None | None | None | N |
| R/M | 0.4547 | ambiguous | 0.4175 | ambiguous | -0.542 | Destabilizing | 1.0 | D | 0.628 | neutral | N | 0.506648442 | None | None | N |
| R/N | 0.7132 | likely_pathogenic | 0.6676 | pathogenic | -0.746 | Destabilizing | 0.985 | D | 0.543 | neutral | None | None | None | None | N |
| R/P | 0.9876 | likely_pathogenic | 0.9818 | pathogenic | -0.796 | Destabilizing | 0.999 | D | 0.68 | prob.neutral | None | None | None | None | N |
| R/Q | 0.1513 | likely_benign | 0.1357 | benign | -1.167 | Destabilizing | 0.97 | D | 0.583 | neutral | None | None | None | None | N |
| R/S | 0.6257 | likely_pathogenic | 0.5459 | ambiguous | -1.491 | Destabilizing | 0.961 | D | 0.569 | neutral | N | 0.370208429 | None | None | N |
| R/T | 0.3915 | ambiguous | 0.3307 | benign | -1.304 | Destabilizing | 0.98 | D | 0.603 | neutral | N | 0.448309427 | None | None | N |
| R/V | 0.569 | likely_pathogenic | 0.5195 | ambiguous | -0.796 | Destabilizing | 0.996 | D | 0.659 | neutral | None | None | None | None | N |
| R/W | 0.348 | ambiguous | 0.3484 | ambiguous | -1.233 | Destabilizing | 1.0 | D | 0.743 | deleterious | N | 0.497490241 | None | None | N |
| R/Y | 0.5122 | ambiguous | 0.5018 | ambiguous | -0.87 | Destabilizing | 0.999 | D | 0.682 | prob.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.