Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25324 | 76195;76196;76197 | chr2:178570162;178570161;178570160 | chr2:179434889;179434888;179434887 |
| N2AB | 23683 | 71272;71273;71274 | chr2:178570162;178570161;178570160 | chr2:179434889;179434888;179434887 |
| N2A | 22756 | 68491;68492;68493 | chr2:178570162;178570161;178570160 | chr2:179434889;179434888;179434887 |
| N2B | 16259 | 49000;49001;49002 | chr2:178570162;178570161;178570160 | chr2:179434889;179434888;179434887 |
| Novex-1 | 16384 | 49375;49376;49377 | chr2:178570162;178570161;178570160 | chr2:179434889;179434888;179434887 |
| Novex-2 | 16451 | 49576;49577;49578 | chr2:178570162;178570161;178570160 | chr2:179434889;179434888;179434887 |
| 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 | rs1369489276  |
-2.074 | 0.91 | N | 0.394 | 0.222 | 0.527908583987 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 9.29E-05 | 0 | 0 |
| V/A | rs1369489276 |
-2.074 | 0.91 | N | 0.394 | 0.222 | 0.527908583987 | gnomAD-4.0.0 | 9.55079E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.12952E-04 | 0 | 0 | 0 | 0 |
| V/L | None | None | 0.835 | N | 0.405 | 0.198 | 0.536616348568 | gnomAD-4.0.0 | 1.59177E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85925E-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 | 0.173 | likely_benign | 0.1894 | benign | -1.727 | Destabilizing | 0.91 | D | 0.394 | neutral | N | 0.397632678 | None | None | N |
| V/C | 0.57 | likely_pathogenic | 0.6464 | pathogenic | -1.137 | Destabilizing | 1.0 | D | 0.597 | neutral | None | None | None | None | N |
| V/D | 0.6079 | likely_pathogenic | 0.6016 | pathogenic | -2.322 | Highly Destabilizing | 0.996 | D | 0.691 | prob.neutral | None | None | None | None | N |
| V/E | 0.4639 | ambiguous | 0.4362 | ambiguous | -2.176 | Highly Destabilizing | 0.994 | D | 0.6 | neutral | N | 0.376755973 | None | None | N |
| V/F | 0.2122 | likely_benign | 0.2318 | benign | -1.043 | Destabilizing | 0.996 | D | 0.563 | neutral | None | None | None | None | N |
| V/G | 0.2274 | likely_benign | 0.2676 | benign | -2.181 | Highly Destabilizing | 0.994 | D | 0.648 | neutral | N | 0.418354667 | None | None | N |
| V/H | 0.6195 | likely_pathogenic | 0.6629 | pathogenic | -1.985 | Destabilizing | 1.0 | D | 0.756 | deleterious | None | None | None | None | N |
| V/I | 0.0795 | likely_benign | 0.0867 | benign | -0.501 | Destabilizing | 0.248 | N | 0.222 | neutral | N | 0.460529363 | None | None | N |
| V/K | 0.549 | ambiguous | 0.5347 | ambiguous | -1.621 | Destabilizing | 0.991 | D | 0.603 | neutral | None | None | None | None | N |
| V/L | 0.1888 | likely_benign | 0.2114 | benign | -0.501 | Destabilizing | 0.835 | D | 0.405 | neutral | N | 0.436767069 | None | None | N |
| V/M | 0.1276 | likely_benign | 0.1539 | benign | -0.415 | Destabilizing | 0.996 | D | 0.466 | neutral | None | None | None | None | N |
| V/N | 0.2946 | likely_benign | 0.3209 | benign | -1.723 | Destabilizing | 0.996 | D | 0.705 | prob.neutral | None | None | None | None | N |
| V/P | 0.9614 | likely_pathogenic | 0.9615 | pathogenic | -0.88 | Destabilizing | 0.999 | D | 0.654 | neutral | None | None | None | None | N |
| V/Q | 0.3882 | ambiguous | 0.4075 | ambiguous | -1.686 | Destabilizing | 0.999 | D | 0.695 | prob.neutral | None | None | None | None | N |
| V/R | 0.4923 | ambiguous | 0.4763 | ambiguous | -1.302 | Destabilizing | 0.996 | D | 0.743 | deleterious | None | None | None | None | N |
| V/S | 0.1698 | likely_benign | 0.1918 | benign | -2.237 | Highly Destabilizing | 0.942 | D | 0.531 | neutral | None | None | None | None | N |
| V/T | 0.1283 | likely_benign | 0.1405 | benign | -1.975 | Destabilizing | 0.155 | N | 0.209 | neutral | None | None | None | None | N |
| V/W | 0.8699 | likely_pathogenic | 0.9027 | pathogenic | -1.561 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | N |
| V/Y | 0.6114 | likely_pathogenic | 0.6652 | pathogenic | -1.158 | Destabilizing | 0.999 | D | 0.592 | 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.