Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26469 | 79630;79631;79632 | chr2:178566727;178566726;178566725 | chr2:179431454;179431453;179431452 |
| N2AB | 24828 | 74707;74708;74709 | chr2:178566727;178566726;178566725 | chr2:179431454;179431453;179431452 |
| N2A | 23901 | 71926;71927;71928 | chr2:178566727;178566726;178566725 | chr2:179431454;179431453;179431452 |
| N2B | 17404 | 52435;52436;52437 | chr2:178566727;178566726;178566725 | chr2:179431454;179431453;179431452 |
| Novex-1 | 17529 | 52810;52811;52812 | chr2:178566727;178566726;178566725 | chr2:179431454;179431453;179431452 |
| Novex-2 | 17596 | 53011;53012;53013 | chr2:178566727;178566726;178566725 | chr2:179431454;179431453;179431452 |
| 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 | 0.517 | N | 0.585 | 0.217 | 0.416075642716 | gnomAD-4.0.0 | 1.592E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02572E-05 |
| V/I | rs540254651  |
-0.707 | 0.003 | N | 0.243 | 0.022 | 0.176091768786 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 4.82E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs540254651 |
-0.707 | 0.003 | N | 0.243 | 0.022 | 0.176091768786 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| V/I | rs540254651 |
-0.707 | 0.003 | N | 0.243 | 0.022 | 0.176091768786 | gnomAD-4.0.0 | 8.11889E-06 | None | None | None | None | N | None | 3.48663E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 7.22972E-06 | 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 | 0.1352 | likely_benign | 0.1458 | benign | -1.147 | Destabilizing | 0.517 | D | 0.585 | neutral | N | 0.515129065 | None | None | N |
| V/C | 0.6193 | likely_pathogenic | 0.6466 | pathogenic | -0.826 | Destabilizing | 0.996 | D | 0.755 | deleterious | None | None | None | None | N |
| V/D | 0.5261 | ambiguous | 0.5884 | pathogenic | -0.816 | Destabilizing | 0.983 | D | 0.831 | deleterious | N | 0.484251892 | None | None | N |
| V/E | 0.4003 | ambiguous | 0.4591 | ambiguous | -0.89 | Destabilizing | 0.987 | D | 0.825 | deleterious | None | None | None | None | N |
| V/F | 0.1758 | likely_benign | 0.2101 | benign | -1.089 | Destabilizing | 0.901 | D | 0.777 | deleterious | N | 0.513955629 | None | None | N |
| V/G | 0.2592 | likely_benign | 0.3017 | benign | -1.373 | Destabilizing | 0.949 | D | 0.815 | deleterious | N | 0.487734612 | None | None | N |
| V/H | 0.6256 | likely_pathogenic | 0.6801 | pathogenic | -0.812 | Destabilizing | 0.996 | D | 0.828 | deleterious | None | None | None | None | N |
| V/I | 0.0604 | likely_benign | 0.0613 | benign | -0.667 | Destabilizing | 0.003 | N | 0.243 | neutral | N | 0.456408836 | None | None | N |
| V/K | 0.5282 | ambiguous | 0.5831 | pathogenic | -0.845 | Destabilizing | 0.961 | D | 0.824 | deleterious | None | None | None | None | N |
| V/L | 0.1417 | likely_benign | 0.1749 | benign | -0.667 | Destabilizing | 0.003 | N | 0.294 | neutral | N | 0.445210407 | None | None | N |
| V/M | 0.1231 | likely_benign | 0.138 | benign | -0.486 | Destabilizing | 0.923 | D | 0.693 | prob.neutral | None | None | None | None | N |
| V/N | 0.3004 | likely_benign | 0.3228 | benign | -0.554 | Destabilizing | 0.987 | D | 0.832 | deleterious | None | None | None | None | N |
| V/P | 0.3331 | likely_benign | 0.3853 | ambiguous | -0.791 | Destabilizing | 0.987 | D | 0.825 | deleterious | None | None | None | None | N |
| V/Q | 0.3869 | ambiguous | 0.4366 | ambiguous | -0.832 | Destabilizing | 0.987 | D | 0.829 | deleterious | None | None | None | None | N |
| V/R | 0.4636 | ambiguous | 0.5258 | ambiguous | -0.245 | Destabilizing | 0.961 | D | 0.831 | deleterious | None | None | None | None | N |
| V/S | 0.2113 | likely_benign | 0.2389 | benign | -1.035 | Destabilizing | 0.961 | D | 0.8 | deleterious | None | None | None | None | N |
| V/T | 0.1238 | likely_benign | 0.1245 | benign | -1.006 | Destabilizing | 0.775 | D | 0.619 | neutral | None | None | None | None | N |
| V/W | 0.7668 | likely_pathogenic | 0.8172 | pathogenic | -1.145 | Destabilizing | 0.996 | D | 0.815 | deleterious | None | None | None | None | N |
| V/Y | 0.5629 | ambiguous | 0.6178 | pathogenic | -0.875 | Destabilizing | 0.961 | D | 0.767 | deleterious | 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.