Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25573 | 76942;76943;76944 | chr2:178569415;178569414;178569413 | chr2:179434142;179434141;179434140 |
| N2AB | 23932 | 72019;72020;72021 | chr2:178569415;178569414;178569413 | chr2:179434142;179434141;179434140 |
| N2A | 23005 | 69238;69239;69240 | chr2:178569415;178569414;178569413 | chr2:179434142;179434141;179434140 |
| N2B | 16508 | 49747;49748;49749 | chr2:178569415;178569414;178569413 | chr2:179434142;179434141;179434140 |
| Novex-1 | 16633 | 50122;50123;50124 | chr2:178569415;178569414;178569413 | chr2:179434142;179434141;179434140 |
| Novex-2 | 16700 | 50323;50324;50325 | chr2:178569415;178569414;178569413 | chr2:179434142;179434141;179434140 |
| 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/L | rs760052770  |
None | 1.0 | N | 0.605 | 0.39 | 0.32580497728 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/L | rs760052770 |
None | 1.0 | N | 0.605 | 0.39 | 0.32580497728 | gnomAD-4.0.0 | 6.57609E-06 | None | None | None | None | I | None | 2.41336E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs760052770 |
0.325 | 1.0 | N | 0.718 | 0.326 | 0.211220785272 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 1.78E-05 | 0 |
| R/Q | rs760052770 |
0.325 | 1.0 | N | 0.718 | 0.326 | 0.211220785272 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 4.83E-05 | 0 | 0 | 0 | 3.86997E-04 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/Q | rs760052770 |
0.325 | 1.0 | N | 0.718 | 0.326 | 0.211220785272 | gnomAD-4.0.0 | 1.85967E-05 | None | None | None | None | I | None | 2.67101E-05 | 0 | None | 0 | 3.5727E-04 | None | 0 | 0 | 8.47761E-06 | 0 | 3.20359E-05 |
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 | 0.9669 | likely_pathogenic | 0.9754 | pathogenic | -0.082 | Destabilizing | 0.999 | D | 0.639 | neutral | None | None | None | None | I |
| R/C | 0.6635 | likely_pathogenic | 0.7457 | pathogenic | -0.113 | Destabilizing | 1.0 | D | 0.758 | deleterious | None | None | None | None | I |
| R/D | 0.9956 | likely_pathogenic | 0.9961 | pathogenic | -0.056 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | I |
| R/E | 0.9656 | likely_pathogenic | 0.9708 | pathogenic | 0.044 | Stabilizing | 0.999 | D | 0.681 | prob.neutral | None | None | None | None | I |
| R/F | 0.9827 | likely_pathogenic | 0.9863 | pathogenic | -0.174 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | I |
| R/G | 0.9558 | likely_pathogenic | 0.9633 | pathogenic | -0.328 | Destabilizing | 1.0 | D | 0.605 | neutral | N | 0.484369434 | None | None | I |
| R/H | 0.5224 | ambiguous | 0.6025 | pathogenic | -1.033 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | I |
| R/I | 0.8845 | likely_pathogenic | 0.9029 | pathogenic | 0.545 | Stabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | I |
| R/K | 0.4527 | ambiguous | 0.5007 | ambiguous | -0.084 | Destabilizing | 0.998 | D | 0.595 | neutral | None | None | None | None | I |
| R/L | 0.8828 | likely_pathogenic | 0.8953 | pathogenic | 0.545 | Stabilizing | 1.0 | D | 0.605 | neutral | N | 0.453575293 | None | None | I |
| R/M | 0.9422 | likely_pathogenic | 0.9556 | pathogenic | 0.03 | Stabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | I |
| R/N | 0.9849 | likely_pathogenic | 0.9869 | pathogenic | 0.154 | Stabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | I |
| R/P | 0.9767 | likely_pathogenic | 0.9817 | pathogenic | 0.358 | Stabilizing | 1.0 | D | 0.693 | prob.neutral | N | 0.501383403 | None | None | I |
| R/Q | 0.5476 | ambiguous | 0.6212 | pathogenic | 0.112 | Stabilizing | 1.0 | D | 0.718 | prob.delet. | N | 0.4770256 | None | None | I |
| R/S | 0.981 | likely_pathogenic | 0.9852 | pathogenic | -0.216 | Destabilizing | 1.0 | D | 0.66 | neutral | None | None | None | None | I |
| R/T | 0.9622 | likely_pathogenic | 0.9697 | pathogenic | 0.044 | Stabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | I |
| R/V | 0.9321 | likely_pathogenic | 0.9472 | pathogenic | 0.358 | Stabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | I |
| R/W | 0.8194 | likely_pathogenic | 0.8515 | pathogenic | -0.187 | Destabilizing | 1.0 | D | 0.774 | deleterious | None | None | None | None | I |
| R/Y | 0.9285 | likely_pathogenic | 0.9434 | pathogenic | 0.207 | Stabilizing | 1.0 | D | 0.722 | prob.delet. | 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.