Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22704 | 68335;68336;68337 | chr2:178578920;178578919;178578918 | chr2:179443647;179443646;179443645 |
| N2AB | 21063 | 63412;63413;63414 | chr2:178578920;178578919;178578918 | chr2:179443647;179443646;179443645 |
| N2A | 20136 | 60631;60632;60633 | chr2:178578920;178578919;178578918 | chr2:179443647;179443646;179443645 |
| N2B | 13639 | 41140;41141;41142 | chr2:178578920;178578919;178578918 | chr2:179443647;179443646;179443645 |
| Novex-1 | 13764 | 41515;41516;41517 | chr2:178578920;178578919;178578918 | chr2:179443647;179443646;179443645 |
| Novex-2 | 13831 | 41716;41717;41718 | chr2:178578920;178578919;178578918 | chr2:179443647;179443646;179443645 |
| 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/G | rs1393414222  |
-0.596 | 0.805 | N | 0.604 | 0.315 | 0.468168183122 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| R/G | rs1393414222 |
-0.596 | 0.805 | N | 0.604 | 0.315 | 0.468168183122 | gnomAD-4.0.0 | 1.59222E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43291E-05 | 0 |
| R/K | rs773477768 |
-0.094 | 0.773 | N | 0.556 | 0.215 | 0.277730125212 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| R/K | rs773477768 |
-0.094 | 0.773 | N | 0.556 | 0.215 | 0.277730125212 | gnomAD-4.0.0 | 1.59222E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43291E-05 | 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 | 0.8756 | likely_pathogenic | 0.7431 | pathogenic | -0.974 | Destabilizing | 0.916 | D | 0.629 | neutral | None | None | None | None | N |
| R/C | 0.4862 | ambiguous | 0.2968 | benign | -0.981 | Destabilizing | 0.999 | D | 0.741 | deleterious | None | None | None | None | N |
| R/D | 0.963 | likely_pathogenic | 0.9195 | pathogenic | -0.061 | Destabilizing | 0.95 | D | 0.626 | neutral | None | None | None | None | N |
| R/E | 0.8572 | likely_pathogenic | 0.7056 | pathogenic | 0.068 | Stabilizing | 0.916 | D | 0.589 | neutral | None | None | None | None | N |
| R/F | 0.8963 | likely_pathogenic | 0.7901 | pathogenic | -0.837 | Destabilizing | 0.996 | D | 0.728 | prob.delet. | None | None | None | None | N |
| R/G | 0.8213 | likely_pathogenic | 0.6558 | pathogenic | -1.278 | Destabilizing | 0.805 | D | 0.604 | neutral | N | 0.471293106 | None | None | N |
| R/H | 0.2615 | likely_benign | 0.1417 | benign | -1.522 | Destabilizing | 0.987 | D | 0.677 | prob.neutral | None | None | None | None | N |
| R/I | 0.6788 | likely_pathogenic | 0.5267 | ambiguous | -0.157 | Destabilizing | 0.983 | D | 0.724 | prob.delet. | N | 0.498796963 | None | None | N |
| R/K | 0.2086 | likely_benign | 0.1309 | benign | -0.911 | Destabilizing | 0.773 | D | 0.556 | neutral | N | 0.419797462 | None | None | N |
| R/L | 0.6346 | likely_pathogenic | 0.4693 | ambiguous | -0.157 | Destabilizing | 0.987 | D | 0.621 | neutral | None | None | None | None | N |
| R/M | 0.7148 | likely_pathogenic | 0.5408 | ambiguous | -0.499 | Destabilizing | 0.999 | D | 0.707 | prob.neutral | None | None | None | None | N |
| R/N | 0.9365 | likely_pathogenic | 0.8528 | pathogenic | -0.419 | Destabilizing | 0.033 | N | 0.395 | neutral | None | None | None | None | N |
| R/P | 0.9081 | likely_pathogenic | 0.8471 | pathogenic | -0.409 | Destabilizing | 0.996 | D | 0.729 | prob.delet. | None | None | None | None | N |
| R/Q | 0.3166 | likely_benign | 0.1784 | benign | -0.588 | Destabilizing | 0.975 | D | 0.649 | neutral | None | None | None | None | N |
| R/S | 0.9112 | likely_pathogenic | 0.7986 | pathogenic | -1.256 | Destabilizing | 0.805 | D | 0.632 | neutral | N | 0.490446838 | None | None | N |
| R/T | 0.73 | likely_pathogenic | 0.5035 | ambiguous | -0.941 | Destabilizing | 0.892 | D | 0.657 | neutral | N | 0.421042681 | None | None | N |
| R/V | 0.7568 | likely_pathogenic | 0.6047 | pathogenic | -0.409 | Destabilizing | 0.987 | D | 0.732 | prob.delet. | None | None | None | None | N |
| R/W | 0.4503 | ambiguous | 0.3009 | benign | -0.465 | Destabilizing | 0.999 | D | 0.727 | prob.delet. | None | None | None | None | N |
| R/Y | 0.7793 | likely_pathogenic | 0.6189 | pathogenic | -0.184 | Destabilizing | 0.996 | D | 0.734 | prob.delet. | 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.