Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17596 | 53011;53012;53013 | chr2:178608001;178608000;178607999 | chr2:179472728;179472727;179472726 |
| N2AB | 15955 | 48088;48089;48090 | chr2:178608001;178608000;178607999 | chr2:179472728;179472727;179472726 |
| N2A | 15028 | 45307;45308;45309 | chr2:178608001;178608000;178607999 | chr2:179472728;179472727;179472726 |
| N2B | 8531 | 25816;25817;25818 | chr2:178608001;178608000;178607999 | chr2:179472728;179472727;179472726 |
| Novex-1 | 8656 | 26191;26192;26193 | chr2:178608001;178608000;178607999 | chr2:179472728;179472727;179472726 |
| Novex-2 | 8723 | 26392;26393;26394 | chr2:178608001;178608000;178607999 | chr2:179472728;179472727;179472726 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/K | rs375966756  |
0.042 | 0.994 | N | 0.629 | 0.285 | 0.195762928549 | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.35E-05 | 1.40726E-04 |
| N/K | rs375966756 |
0.042 | 0.994 | N | 0.629 | 0.285 | 0.195762928549 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 7.36E-05 | 0 | 0 |
| N/K | rs375966756 |
0.042 | 0.994 | N | 0.629 | 0.285 | 0.195762928549 | gnomAD-4.0.0 | 1.73603E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.20466E-05 | 0 | 3.2041E-05 |
| N/S | rs760584088 |
-0.733 | 0.978 | N | 0.552 | 0.175 | 0.239305524855 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| N/S | rs760584088 |
-0.733 | 0.978 | N | 0.552 | 0.175 | 0.239305524855 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| N/S | rs760584088 |
-0.733 | 0.978 | N | 0.552 | 0.175 | 0.239305524855 | gnomAD-4.0.0 | 2.17018E-05 | None | None | None | None | I | None | 1.33622E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.6286E-05 | 0 | 4.80769E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.4009 | ambiguous | 0.388 | ambiguous | -1.021 | Destabilizing | 0.992 | D | 0.677 | prob.neutral | None | None | None | None | I |
| N/C | 0.4152 | ambiguous | 0.3754 | ambiguous | -0.046 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | I |
| N/D | 0.1208 | likely_benign | 0.1084 | benign | -0.348 | Destabilizing | 0.994 | D | 0.567 | neutral | N | 0.408174959 | None | None | I |
| N/E | 0.6412 | likely_pathogenic | 0.6306 | pathogenic | -0.283 | Destabilizing | 0.996 | D | 0.625 | neutral | None | None | None | None | I |
| N/F | 0.7819 | likely_pathogenic | 0.7794 | pathogenic | -0.946 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | I |
| N/G | 0.4447 | ambiguous | 0.4284 | ambiguous | -1.319 | Destabilizing | 0.996 | D | 0.578 | neutral | None | None | None | None | I |
| N/H | 0.2256 | likely_benign | 0.2313 | benign | -1.076 | Destabilizing | 0.999 | D | 0.689 | prob.neutral | N | 0.471190974 | None | None | I |
| N/I | 0.516 | ambiguous | 0.5089 | ambiguous | -0.276 | Destabilizing | 0.997 | D | 0.782 | deleterious | N | 0.506571084 | None | None | I |
| N/K | 0.7049 | likely_pathogenic | 0.6844 | pathogenic | -0.183 | Destabilizing | 0.994 | D | 0.629 | neutral | N | 0.469923526 | None | None | I |
| N/L | 0.4248 | ambiguous | 0.442 | ambiguous | -0.276 | Destabilizing | 0.998 | D | 0.725 | prob.delet. | None | None | None | None | I |
| N/M | 0.6374 | likely_pathogenic | 0.6392 | pathogenic | 0.306 | Stabilizing | 1.0 | D | 0.744 | deleterious | None | None | None | None | I |
| N/P | 0.6287 | likely_pathogenic | 0.6002 | pathogenic | -0.496 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | I |
| N/Q | 0.612 | likely_pathogenic | 0.5974 | pathogenic | -0.837 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | I |
| N/R | 0.643 | likely_pathogenic | 0.6218 | pathogenic | -0.143 | Destabilizing | 0.999 | D | 0.669 | neutral | None | None | None | None | I |
| N/S | 0.0861 | likely_benign | 0.0848 | benign | -0.817 | Destabilizing | 0.978 | D | 0.552 | neutral | N | 0.502970632 | None | None | I |
| N/T | 0.1607 | likely_benign | 0.1624 | benign | -0.559 | Destabilizing | 0.543 | D | 0.205 | neutral | N | 0.485905023 | None | None | I |
| N/V | 0.4804 | ambiguous | 0.4779 | ambiguous | -0.496 | Destabilizing | 0.998 | D | 0.715 | prob.delet. | None | None | None | None | I |
| N/W | 0.9025 | likely_pathogenic | 0.8956 | pathogenic | -0.665 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | I |
| N/Y | 0.3714 | ambiguous | 0.3588 | ambiguous | -0.481 | Destabilizing | 0.999 | D | 0.767 | deleterious | N | 0.490055697 | 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.