Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27053 | 81382;81383;81384 | chr2:178564975;178564974;178564973 | chr2:179429702;179429701;179429700 |
| N2AB | 25412 | 76459;76460;76461 | chr2:178564975;178564974;178564973 | chr2:179429702;179429701;179429700 |
| N2A | 24485 | 73678;73679;73680 | chr2:178564975;178564974;178564973 | chr2:179429702;179429701;179429700 |
| N2B | 17988 | 54187;54188;54189 | chr2:178564975;178564974;178564973 | chr2:179429702;179429701;179429700 |
| Novex-1 | 18113 | 54562;54563;54564 | chr2:178564975;178564974;178564973 | chr2:179429702;179429701;179429700 |
| Novex-2 | 18180 | 54763;54764;54765 | chr2:178564975;178564974;178564973 | chr2:179429702;179429701;179429700 |
| 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/N | rs776943572  |
0.028 | 0.983 | N | 0.656 | 0.414 | 0.36076525451 | gnomAD-2.1.1 | 8.98E-05 | None | None | None | None | I | None | 0 | 6.85127E-04 | None | 9.79E-05 | 0 | None | 0 | None | 0 | 0 | 0 |
| Y/N | rs776943572 |
0.028 | 0.983 | N | 0.656 | 0.414 | 0.36076525451 | gnomAD-3.1.2 | 1.31525E-04 | None | None | None | None | I | None | 2.41E-05 | 1.04781E-03 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 9.56938E-04 |
| Y/N | rs776943572 |
0.028 | 0.983 | N | 0.656 | 0.414 | 0.36076525451 | gnomAD-4.0.0 | 4.46737E-05 | None | None | None | None | I | None | 1.33926E-05 | 7.87191E-04 | None | 3.38776E-05 | 0 | None | 0 | 0 | 1.27229E-05 | 0 | 1.28283E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.9744 | likely_pathogenic | 0.9785 | pathogenic | -0.618 | Destabilizing | 0.916 | D | 0.633 | neutral | None | None | None | None | I |
| Y/C | 0.6855 | likely_pathogenic | 0.7301 | pathogenic | 0.219 | Stabilizing | 0.999 | D | 0.683 | prob.neutral | D | 0.522655257 | None | None | I |
| Y/D | 0.9798 | likely_pathogenic | 0.9786 | pathogenic | 0.758 | Stabilizing | 0.994 | D | 0.669 | neutral | N | 0.486760334 | None | None | I |
| Y/E | 0.9938 | likely_pathogenic | 0.9937 | pathogenic | 0.736 | Stabilizing | 0.987 | D | 0.651 | neutral | None | None | None | None | I |
| Y/F | 0.1553 | likely_benign | 0.1446 | benign | -0.323 | Destabilizing | 0.892 | D | 0.557 | neutral | N | 0.46133744 | None | None | I |
| Y/G | 0.9563 | likely_pathogenic | 0.9588 | pathogenic | -0.806 | Destabilizing | 0.987 | D | 0.653 | neutral | None | None | None | None | I |
| Y/H | 0.8246 | likely_pathogenic | 0.8073 | pathogenic | 0.224 | Stabilizing | 0.994 | D | 0.607 | neutral | N | 0.468936021 | None | None | I |
| Y/I | 0.932 | likely_pathogenic | 0.9482 | pathogenic | -0.145 | Destabilizing | 0.95 | D | 0.618 | neutral | None | None | None | None | I |
| Y/K | 0.986 | likely_pathogenic | 0.9856 | pathogenic | 0.253 | Stabilizing | 0.975 | D | 0.645 | neutral | None | None | None | None | I |
| Y/L | 0.8604 | likely_pathogenic | 0.8823 | pathogenic | -0.145 | Destabilizing | 0.437 | N | 0.6 | neutral | None | None | None | None | I |
| Y/M | 0.9414 | likely_pathogenic | 0.9507 | pathogenic | -0.034 | Destabilizing | 0.693 | D | 0.554 | neutral | None | None | None | None | I |
| Y/N | 0.8953 | likely_pathogenic | 0.8904 | pathogenic | 0.073 | Stabilizing | 0.983 | D | 0.656 | neutral | N | 0.471213746 | None | None | I |
| Y/P | 0.9968 | likely_pathogenic | 0.9959 | pathogenic | -0.284 | Destabilizing | 0.996 | D | 0.685 | prob.neutral | None | None | None | None | I |
| Y/Q | 0.9822 | likely_pathogenic | 0.981 | pathogenic | 0.106 | Stabilizing | 0.987 | D | 0.62 | neutral | None | None | None | None | I |
| Y/R | 0.96 | likely_pathogenic | 0.9595 | pathogenic | 0.496 | Stabilizing | 0.987 | D | 0.657 | neutral | None | None | None | None | I |
| Y/S | 0.9363 | likely_pathogenic | 0.941 | pathogenic | -0.309 | Destabilizing | 0.967 | D | 0.601 | neutral | N | 0.473290888 | None | None | I |
| Y/T | 0.9817 | likely_pathogenic | 0.9831 | pathogenic | -0.238 | Destabilizing | 0.975 | D | 0.633 | neutral | None | None | None | None | I |
| Y/V | 0.9009 | likely_pathogenic | 0.9203 | pathogenic | -0.284 | Destabilizing | 0.845 | D | 0.641 | neutral | None | None | None | None | I |
| Y/W | 0.7184 | likely_pathogenic | 0.7073 | pathogenic | -0.463 | Destabilizing | 0.999 | D | 0.593 | 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.