Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33428 | 100507;100508;100509 | chr2:178536465;178536464;178536463 | chr2:179401192;179401191;179401190 |
| N2AB | 31787 | 95584;95585;95586 | chr2:178536465;178536464;178536463 | chr2:179401192;179401191;179401190 |
| N2A | 30860 | 92803;92804;92805 | chr2:178536465;178536464;178536463 | chr2:179401192;179401191;179401190 |
| N2B | 24363 | 73312;73313;73314 | chr2:178536465;178536464;178536463 | chr2:179401192;179401191;179401190 |
| Novex-1 | 24488 | 73687;73688;73689 | chr2:178536465;178536464;178536463 | chr2:179401192;179401191;179401190 |
| Novex-2 | 24555 | 73888;73889;73890 | chr2:178536465;178536464;178536463 | chr2:179401192;179401191;179401190 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/H | rs766455406  |
-1.67 | 0.983 | N | 0.64 | 0.368 | 0.331619326243 | gnomAD-2.1.1 | 3.18E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| Y/N | rs766455406 |
-2.381 | 0.983 | N | 0.732 | 0.548 | 0.608268572844 | gnomAD-2.1.1 | 4.2E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.22E-06 | 0 |
| Y/N | rs766455406 |
-2.381 | 0.983 | N | 0.732 | 0.548 | 0.608268572844 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| Y/N | rs766455406 |
-2.381 | 0.983 | N | 0.732 | 0.548 | 0.608268572844 | gnomAD-4.0.0 | 1.31106E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.78958E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.4777 | ambiguous | 0.4019 | ambiguous | -2.422 | Highly Destabilizing | 0.775 | D | 0.649 | neutral | None | None | None | None | I |
| Y/C | 0.1158 | likely_benign | 0.0893 | benign | -0.973 | Destabilizing | 0.041 | N | 0.587 | neutral | N | 0.438788654 | None | None | I |
| Y/D | 0.4367 | ambiguous | 0.3998 | ambiguous | -1.434 | Destabilizing | 0.983 | D | 0.74 | deleterious | N | 0.459219854 | None | None | I |
| Y/E | 0.6823 | likely_pathogenic | 0.6324 | pathogenic | -1.312 | Destabilizing | 0.987 | D | 0.739 | prob.delet. | None | None | None | None | I |
| Y/F | 0.0828 | likely_benign | 0.0653 | benign | -0.905 | Destabilizing | 0.008 | N | 0.265 | neutral | N | 0.401731776 | None | None | I |
| Y/G | 0.5233 | ambiguous | 0.4701 | ambiguous | -2.763 | Highly Destabilizing | 0.961 | D | 0.721 | prob.delet. | None | None | None | None | I |
| Y/H | 0.136 | likely_benign | 0.1194 | benign | -1.067 | Destabilizing | 0.983 | D | 0.64 | neutral | N | 0.447157421 | None | None | I |
| Y/I | 0.2616 | likely_benign | 0.2357 | benign | -1.353 | Destabilizing | 0.858 | D | 0.672 | neutral | None | None | None | None | I |
| Y/K | 0.4864 | ambiguous | 0.4768 | ambiguous | -1.386 | Destabilizing | 0.961 | D | 0.738 | prob.delet. | None | None | None | None | I |
| Y/L | 0.3416 | ambiguous | 0.3119 | benign | -1.353 | Destabilizing | 0.633 | D | 0.607 | neutral | None | None | None | None | I |
| Y/M | 0.5522 | ambiguous | 0.482 | ambiguous | -0.949 | Destabilizing | 0.989 | D | 0.713 | prob.delet. | None | None | None | None | I |
| Y/N | 0.2046 | likely_benign | 0.178 | benign | -1.837 | Destabilizing | 0.983 | D | 0.732 | prob.delet. | N | 0.443789042 | None | None | I |
| Y/P | 0.9808 | likely_pathogenic | 0.983 | pathogenic | -1.71 | Destabilizing | 0.987 | D | 0.742 | deleterious | None | None | None | None | I |
| Y/Q | 0.4261 | ambiguous | 0.363 | ambiguous | -1.722 | Destabilizing | 0.987 | D | 0.717 | prob.delet. | None | None | None | None | I |
| Y/R | 0.3039 | likely_benign | 0.296 | benign | -0.975 | Destabilizing | 0.961 | D | 0.729 | prob.delet. | None | None | None | None | I |
| Y/S | 0.1942 | likely_benign | 0.1729 | benign | -2.321 | Highly Destabilizing | 0.949 | D | 0.703 | prob.neutral | N | 0.436188279 | None | None | I |
| Y/T | 0.3298 | likely_benign | 0.2861 | benign | -2.102 | Highly Destabilizing | 0.961 | D | 0.711 | prob.delet. | None | None | None | None | I |
| Y/V | 0.2509 | likely_benign | 0.2207 | benign | -1.71 | Destabilizing | 0.633 | D | 0.627 | neutral | None | None | None | None | I |
| Y/W | 0.4444 | ambiguous | 0.4037 | ambiguous | -0.399 | Destabilizing | 0.996 | D | 0.642 | 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.