Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35953 | 108082;108083;108084 | chr2:178527131;178527130;178527129 | chr2:179391858;179391857;179391856 |
| N2AB | 34312 | 103159;103160;103161 | chr2:178527131;178527130;178527129 | chr2:179391858;179391857;179391856 |
| N2A | 33385 | 100378;100379;100380 | chr2:178527131;178527130;178527129 | chr2:179391858;179391857;179391856 |
| N2B | 26888 | 80887;80888;80889 | chr2:178527131;178527130;178527129 | chr2:179391858;179391857;179391856 |
| Novex-1 | 27013 | 81262;81263;81264 | chr2:178527131;178527130;178527129 | chr2:179391858;179391857;179391856 |
| Novex-2 | 27080 | 81463;81464;81465 | chr2:178527131;178527130;178527129 | chr2:179391858;179391857;179391856 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/M | None | None | 0.997 | N | 0.641 | 0.213 | 0.567280287869 | gnomAD-4.0.0 | 1.59092E-06 | None | None | None | -0.731(OBSL1) -0.865(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43271E-05 | 0 |
| L/R | rs794729572  |
None | 0.999 | N | 0.743 | 0.499 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | -1.961(OBSL1) -1.67(OBSCN) | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| L/R | rs794729572 |
None | 0.999 | N | 0.743 | 0.499 | None | gnomAD-4.0.0 | 3.84243E-06 | None | None | None | -1.961(OBSL1) -1.67(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.17724E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.7865 | likely_pathogenic | 0.7864 | pathogenic | -1.538 | Destabilizing | 0.983 | D | 0.557 | neutral | None | None | None | -1.036(OBSL1) -0.636(OBSCN) | N |
| L/C | 0.9139 | likely_pathogenic | 0.9144 | pathogenic | -0.996 | Destabilizing | 1.0 | D | 0.708 | prob.delet. | None | None | None | -0.537(OBSL1) -0.648(OBSCN) | N |
| L/D | 0.9722 | likely_pathogenic | 0.9661 | pathogenic | -1.202 | Destabilizing | 0.999 | D | 0.753 | deleterious | None | None | None | -1.066(OBSL1) -0.686(OBSCN) | N |
| L/E | 0.8524 | likely_pathogenic | 0.8462 | pathogenic | -1.236 | Destabilizing | 0.999 | D | 0.746 | deleterious | None | None | None | -1.237(OBSL1) -0.813(OBSCN) | N |
| L/F | 0.527 | ambiguous | 0.5155 | ambiguous | -1.369 | Destabilizing | 0.296 | N | 0.327 | neutral | None | None | None | -0.802(OBSL1) -0.106(OBSCN) | N |
| L/G | 0.9507 | likely_pathogenic | 0.9419 | pathogenic | -1.811 | Destabilizing | 0.999 | D | 0.74 | deleterious | None | None | None | -0.918(OBSL1) -0.6(OBSCN) | N |
| L/H | 0.7569 | likely_pathogenic | 0.7525 | pathogenic | -1.088 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | -0.868(OBSL1) -0.42(OBSCN) | N |
| L/I | 0.2119 | likely_benign | 0.2142 | benign | -0.879 | Destabilizing | 0.967 | D | 0.423 | neutral | None | None | None | -1.461(OBSL1) -0.802(OBSCN) | N |
| L/K | 0.7102 | likely_pathogenic | 0.7042 | pathogenic | -0.865 | Destabilizing | 0.999 | D | 0.727 | prob.delet. | None | None | None | -1.78(OBSL1) -1.298(OBSCN) | N |
| L/M | 0.2794 | likely_benign | 0.2828 | benign | -0.601 | Destabilizing | 0.997 | D | 0.641 | neutral | N | 0.50723838 | None | -0.731(OBSL1) -0.865(OBSCN) | N |
| L/N | 0.8888 | likely_pathogenic | 0.8803 | pathogenic | -0.679 | Destabilizing | 0.999 | D | 0.743 | deleterious | None | None | None | -0.767(OBSL1) -0.678(OBSCN) | N |
| L/P | 0.9928 | likely_pathogenic | 0.9892 | pathogenic | -1.068 | Destabilizing | 0.999 | D | 0.744 | deleterious | N | 0.491061608 | None | -1.309(OBSL1) -0.738(OBSCN) | N |
| L/Q | 0.6533 | likely_pathogenic | 0.6548 | pathogenic | -0.953 | Destabilizing | 0.999 | D | 0.735 | prob.delet. | N | 0.493538364 | None | -0.898(OBSL1) -0.665(OBSCN) | N |
| L/R | 0.6246 | likely_pathogenic | 0.6044 | pathogenic | -0.264 | Destabilizing | 0.999 | D | 0.743 | deleterious | N | 0.487996471 | None | -1.961(OBSL1) -1.67(OBSCN) | N |
| L/S | 0.8686 | likely_pathogenic | 0.8676 | pathogenic | -1.261 | Destabilizing | 0.998 | D | 0.714 | prob.delet. | None | None | None | -0.657(OBSL1) -0.375(OBSCN) | N |
| L/T | 0.6983 | likely_pathogenic | 0.6924 | pathogenic | -1.186 | Destabilizing | 0.995 | D | 0.687 | prob.neutral | None | None | None | -0.836(OBSL1) -0.496(OBSCN) | N |
| L/V | 0.2668 | likely_benign | 0.2708 | benign | -1.068 | Destabilizing | 0.37 | N | 0.369 | neutral | N | 0.460753942 | None | -1.309(OBSL1) -0.738(OBSCN) | N |
| L/W | 0.8251 | likely_pathogenic | 0.7918 | pathogenic | -1.406 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | -0.857(OBSL1) -0.308(OBSCN) | N |
| L/Y | 0.8294 | likely_pathogenic | 0.8258 | pathogenic | -1.139 | Destabilizing | 0.99 | D | 0.74 | deleterious | None | None | None | -0.735(OBSL1) -0.255(OBSCN) | 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.