Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14328 | 43207;43208;43209 | chr2:178633291;178633290;178633289 | chr2:179498018;179498017;179498016 |
| N2AB | 12687 | 38284;38285;38286 | chr2:178633291;178633290;178633289 | chr2:179498018;179498017;179498016 |
| N2A | 11760 | 35503;35504;35505 | chr2:178633291;178633290;178633289 | chr2:179498018;179498017;179498016 |
| N2B | 5263 | 16012;16013;16014 | chr2:178633291;178633290;178633289 | chr2:179498018;179498017;179498016 |
| Novex-1 | 5388 | 16387;16388;16389 | chr2:178633291;178633290;178633289 | chr2:179498018;179498017;179498016 |
| Novex-2 | 5455 | 16588;16589;16590 | chr2:178633291;178633290;178633289 | chr2:179498018;179498017;179498016 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | None | None | 0.001 | N | 0.113 | 0.119 | 0.415055319159 | gnomAD-4.0.0 | 3.18451E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.7202E-06 | 0 | 0 |
| V/G | rs2060028786  |
None | 0.22 | D | 0.663 | 0.203 | 0.698599672906 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/G | rs2060028786 |
None | 0.22 | D | 0.663 | 0.203 | 0.698599672906 | gnomAD-4.0.0 | 6.57938E-06 | None | None | None | None | N | None | 2.41534E-05 | 0 | None | 0 | 0 | None | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2121 | likely_benign | 0.1878 | benign | -1.337 | Destabilizing | 0.001 | N | 0.113 | neutral | N | 0.451697312 | None | None | N |
| V/C | 0.826 | likely_pathogenic | 0.8003 | pathogenic | -0.821 | Destabilizing | 0.953 | D | 0.549 | neutral | None | None | None | None | N |
| V/D | 0.6075 | likely_pathogenic | 0.5991 | pathogenic | -1.071 | Destabilizing | 0.724 | D | 0.708 | prob.delet. | None | None | None | None | N |
| V/E | 0.3852 | ambiguous | 0.3943 | ambiguous | -1.005 | Destabilizing | 0.22 | N | 0.646 | neutral | D | 0.570549585 | None | None | N |
| V/F | 0.3053 | likely_benign | 0.2823 | benign | -0.865 | Destabilizing | 0.842 | D | 0.554 | neutral | None | None | None | None | N |
| V/G | 0.3883 | ambiguous | 0.3698 | ambiguous | -1.717 | Destabilizing | 0.22 | N | 0.663 | prob.neutral | D | 0.610000647 | None | None | N |
| V/H | 0.7547 | likely_pathogenic | 0.7508 | pathogenic | -1.302 | Destabilizing | 0.953 | D | 0.725 | deleterious | None | None | None | None | N |
| V/I | 0.0987 | likely_benign | 0.0968 | benign | -0.372 | Destabilizing | 0.361 | N | 0.538 | neutral | N | 0.468089011 | None | None | N |
| V/K | 0.3291 | likely_benign | 0.3461 | ambiguous | -1.052 | Destabilizing | 0.272 | N | 0.635 | neutral | None | None | None | None | N |
| V/L | 0.3489 | ambiguous | 0.3474 | ambiguous | -0.372 | Destabilizing | 0.104 | N | 0.455 | neutral | N | 0.413645491 | None | None | N |
| V/M | 0.1678 | likely_benign | 0.175 | benign | -0.332 | Destabilizing | 0.842 | D | 0.447 | neutral | None | None | None | None | N |
| V/N | 0.4815 | ambiguous | 0.4799 | ambiguous | -0.979 | Destabilizing | 0.724 | D | 0.729 | deleterious | None | None | None | None | N |
| V/P | 0.9337 | likely_pathogenic | 0.9226 | pathogenic | -0.659 | Destabilizing | 0.842 | D | 0.677 | prob.neutral | None | None | None | None | N |
| V/Q | 0.3652 | ambiguous | 0.3866 | ambiguous | -1.025 | Destabilizing | 0.023 | N | 0.481 | neutral | None | None | None | None | N |
| V/R | 0.3209 | likely_benign | 0.338 | benign | -0.707 | Destabilizing | 0.568 | D | 0.732 | deleterious | None | None | None | None | N |
| V/S | 0.3474 | ambiguous | 0.3322 | benign | -1.551 | Destabilizing | 0.272 | N | 0.634 | neutral | None | None | None | None | N |
| V/T | 0.2084 | likely_benign | 0.1872 | benign | -1.362 | Destabilizing | 0.01 | N | 0.281 | neutral | None | None | None | None | N |
| V/W | 0.9309 | likely_pathogenic | 0.9224 | pathogenic | -1.163 | Destabilizing | 0.984 | D | 0.769 | deleterious | None | None | None | None | N |
| V/Y | 0.7733 | likely_pathogenic | 0.7522 | pathogenic | -0.793 | Destabilizing | 0.942 | D | 0.551 | 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.