Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30906 | 92941;92942;92943 | chr2:178548910;178548909;178548908 | chr2:179413637;179413636;179413635 |
| N2AB | 29265 | 88018;88019;88020 | chr2:178548910;178548909;178548908 | chr2:179413637;179413636;179413635 |
| N2A | 28338 | 85237;85238;85239 | chr2:178548910;178548909;178548908 | chr2:179413637;179413636;179413635 |
| N2B | 21841 | 65746;65747;65748 | chr2:178548910;178548909;178548908 | chr2:179413637;179413636;179413635 |
| Novex-1 | 21966 | 66121;66122;66123 | chr2:178548910;178548909;178548908 | chr2:179413637;179413636;179413635 |
| Novex-2 | 22033 | 66322;66323;66324 | chr2:178548910;178548909;178548908 | chr2:179413637;179413636;179413635 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs749379446  |
0.103 | 0.001 | N | 0.233 | 0.079 | 0.0986583533028 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 0 | 0 |
| D/E | rs749379446 |
0.103 | 0.001 | N | 0.233 | 0.079 | 0.0986583533028 | gnomAD-4.0.0 | 1.36837E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79886E-06 | 0 | 0 |
| D/G | None | None | 0.334 | N | 0.621 | 0.304 | 0.198526703765 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.66327E-05 |
| D/N | rs534881266 |
0.583 | 0.739 | N | 0.63 | 0.223 | None | gnomAD-2.1.1 | 5E-05 | None | None | None | None | I | None | 0 | 8.48E-05 | None | 0 | 3.07692E-04 | None | 0 | None | 0 | 2.34E-05 | 2.80741E-04 |
| D/N | rs534881266 |
0.583 | 0.739 | N | 0.63 | 0.223 | None | gnomAD-3.1.2 | 3.94E-05 | None | None | None | None | I | None | 2.41E-05 | 6.55E-05 | 0 | 0 | 1.93125E-04 | None | 0 | 0 | 2.94E-05 | 2.07125E-04 | 0 |
| D/N | rs534881266 |
0.583 | 0.739 | N | 0.63 | 0.223 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| D/N | rs534881266 |
0.583 | 0.739 | N | 0.63 | 0.223 | None | gnomAD-4.0.0 | 4.15152E-05 | None | None | None | None | I | None | 1.33255E-05 | 8.33167E-05 | None | 0 | 4.45911E-05 | None | 0 | 0 | 4.74643E-05 | 1.09796E-05 | 3.20113E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1059 | likely_benign | 0.1144 | benign | -0.201 | Destabilizing | 0.201 | N | 0.595 | neutral | N | 0.438383222 | None | None | I |
| D/C | 0.4087 | ambiguous | 0.4575 | ambiguous | 0.27 | Stabilizing | 0.982 | D | 0.767 | deleterious | None | None | None | None | I |
| D/E | 0.0729 | likely_benign | 0.0755 | benign | -0.29 | Destabilizing | 0.001 | N | 0.233 | neutral | N | 0.335160067 | None | None | I |
| D/F | 0.3968 | ambiguous | 0.432 | ambiguous | -0.366 | Destabilizing | 0.935 | D | 0.727 | prob.delet. | None | None | None | None | I |
| D/G | 0.1254 | likely_benign | 0.1406 | benign | -0.386 | Destabilizing | 0.334 | N | 0.621 | neutral | N | 0.510224678 | None | None | I |
| D/H | 0.2236 | likely_benign | 0.2424 | benign | -0.409 | Destabilizing | 0.972 | D | 0.625 | neutral | N | 0.475216672 | None | None | I |
| D/I | 0.1811 | likely_benign | 0.194 | benign | 0.229 | Stabilizing | 0.826 | D | 0.725 | prob.delet. | None | None | None | None | I |
| D/K | 0.1967 | likely_benign | 0.2133 | benign | 0.395 | Stabilizing | 0.25 | N | 0.599 | neutral | None | None | None | None | I |
| D/L | 0.2165 | likely_benign | 0.2341 | benign | 0.229 | Stabilizing | 0.7 | D | 0.699 | prob.neutral | None | None | None | None | I |
| D/M | 0.37 | ambiguous | 0.3908 | ambiguous | 0.501 | Stabilizing | 0.982 | D | 0.719 | prob.delet. | None | None | None | None | I |
| D/N | 0.0835 | likely_benign | 0.0882 | benign | 0.249 | Stabilizing | 0.739 | D | 0.63 | neutral | N | 0.493025784 | None | None | I |
| D/P | 0.3482 | ambiguous | 0.3787 | ambiguous | 0.108 | Stabilizing | 0.826 | D | 0.635 | neutral | None | None | None | None | I |
| D/Q | 0.1891 | likely_benign | 0.2016 | benign | 0.246 | Stabilizing | 0.539 | D | 0.581 | neutral | None | None | None | None | I |
| D/R | 0.2498 | likely_benign | 0.2685 | benign | 0.402 | Stabilizing | 0.539 | D | 0.674 | neutral | None | None | None | None | I |
| D/S | 0.0963 | likely_benign | 0.105 | benign | 0.121 | Stabilizing | 0.25 | N | 0.577 | neutral | None | None | None | None | I |
| D/T | 0.1506 | likely_benign | 0.1601 | benign | 0.257 | Stabilizing | 0.7 | D | 0.593 | neutral | None | None | None | None | I |
| D/V | 0.1182 | likely_benign | 0.1276 | benign | 0.108 | Stabilizing | 0.638 | D | 0.687 | prob.neutral | N | 0.486657172 | None | None | I |
| D/W | 0.7686 | likely_pathogenic | 0.8039 | pathogenic | -0.31 | Destabilizing | 0.982 | D | 0.749 | deleterious | None | None | None | None | I |
| D/Y | 0.1704 | likely_benign | 0.1873 | benign | -0.142 | Destabilizing | 0.965 | D | 0.727 | prob.delet. | N | 0.487586935 | 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.