Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16788 | 50587;50588;50589 | chr2:178611947;178611946;178611945 | chr2:179476674;179476673;179476672 |
| N2AB | 15147 | 45664;45665;45666 | chr2:178611947;178611946;178611945 | chr2:179476674;179476673;179476672 |
| N2A | 14220 | 42883;42884;42885 | chr2:178611947;178611946;178611945 | chr2:179476674;179476673;179476672 |
| N2B | 7723 | 23392;23393;23394 | chr2:178611947;178611946;178611945 | chr2:179476674;179476673;179476672 |
| Novex-1 | 7848 | 23767;23768;23769 | chr2:178611947;178611946;178611945 | chr2:179476674;179476673;179476672 |
| Novex-2 | 7915 | 23968;23969;23970 | chr2:178611947;178611946;178611945 | chr2:179476674;179476673;179476672 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs397517599  |
-2.96 | 0.98 | D | 0.604 | 0.534 | 0.749266289315 | gnomAD-2.1.1 | 7.89531E-04 | None | None | None | None | N | None | 0 | 5.74E-05 | None | 0 | 0 | None | 6.91949E-03 | None | 0 | 5.51E-05 | 2.83849E-04 |
| I/T | rs397517599 |
-2.96 | 0.98 | D | 0.604 | 0.534 | 0.749266289315 | gnomAD-3.1.2 | 1.64487E-04 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 4.96483E-03 | 0 |
| I/T | rs397517599 |
-2.96 | 0.98 | D | 0.604 | 0.534 | 0.749266289315 | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 2E-03 | None |
| I/T | rs397517599 |
-2.96 | 0.98 | D | 0.604 | 0.534 | 0.749266289315 | gnomAD-4.0.0 | 3.63688E-04 | None | None | None | None | N | None | 1.33722E-05 | 5.03423E-05 | None | 0 | 0 | None | 0 | 3.31236E-04 | 4.24103E-06 | 6.01386E-03 | 4.81155E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9471 | likely_pathogenic | 0.9498 | pathogenic | -2.953 | Highly Destabilizing | 0.985 | D | 0.597 | neutral | None | None | None | None | N |
| I/C | 0.9887 | likely_pathogenic | 0.9872 | pathogenic | -1.942 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| I/D | 0.9998 | likely_pathogenic | 0.9998 | pathogenic | -3.603 | Highly Destabilizing | 0.999 | D | 0.85 | deleterious | None | None | None | None | N |
| I/E | 0.9988 | likely_pathogenic | 0.9989 | pathogenic | -3.276 | Highly Destabilizing | 0.999 | D | 0.843 | deleterious | None | None | None | None | N |
| I/F | 0.8981 | likely_pathogenic | 0.8928 | pathogenic | -1.74 | Destabilizing | 0.994 | D | 0.645 | neutral | D | 0.705615859 | None | None | N |
| I/G | 0.9974 | likely_pathogenic | 0.9976 | pathogenic | -3.564 | Highly Destabilizing | 0.999 | D | 0.837 | deleterious | None | None | None | None | N |
| I/H | 0.9992 | likely_pathogenic | 0.9992 | pathogenic | -3.138 | Highly Destabilizing | 1.0 | D | 0.83 | deleterious | None | None | None | None | N |
| I/K | 0.998 | likely_pathogenic | 0.9979 | pathogenic | -2.289 | Highly Destabilizing | 0.999 | D | 0.842 | deleterious | None | None | None | None | N |
| I/L | 0.4492 | ambiguous | 0.3977 | ambiguous | -1.104 | Destabilizing | 0.061 | N | 0.27 | neutral | N | 0.487007053 | None | None | N |
| I/M | 0.5642 | likely_pathogenic | 0.5544 | ambiguous | -1.168 | Destabilizing | 0.994 | D | 0.625 | neutral | D | 0.569073227 | None | None | N |
| I/N | 0.9972 | likely_pathogenic | 0.9972 | pathogenic | -3.003 | Highly Destabilizing | 0.999 | D | 0.855 | deleterious | D | 0.706851836 | None | None | N |
| I/P | 0.9976 | likely_pathogenic | 0.9977 | pathogenic | -1.713 | Destabilizing | 0.999 | D | 0.858 | deleterious | None | None | None | None | N |
| I/Q | 0.9981 | likely_pathogenic | 0.9982 | pathogenic | -2.659 | Highly Destabilizing | 0.999 | D | 0.865 | deleterious | None | None | None | None | N |
| I/R | 0.9961 | likely_pathogenic | 0.9963 | pathogenic | -2.284 | Highly Destabilizing | 0.999 | D | 0.854 | deleterious | None | None | None | None | N |
| I/S | 0.9896 | likely_pathogenic | 0.9902 | pathogenic | -3.562 | Highly Destabilizing | 0.997 | D | 0.747 | deleterious | D | 0.706851836 | None | None | N |
| I/T | 0.9153 | likely_pathogenic | 0.9075 | pathogenic | -3.074 | Highly Destabilizing | 0.98 | D | 0.604 | neutral | D | 0.705615859 | None | None | N |
| I/V | 0.1247 | likely_benign | 0.1171 | benign | -1.713 | Destabilizing | 0.4 | N | 0.205 | neutral | N | 0.447398307 | None | None | N |
| I/W | 0.9985 | likely_pathogenic | 0.9986 | pathogenic | -2.129 | Highly Destabilizing | 1.0 | D | 0.79 | deleterious | None | None | None | None | N |
| I/Y | 0.9955 | likely_pathogenic | 0.9959 | pathogenic | -1.941 | Destabilizing | 0.999 | D | 0.689 | 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.