Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18644 | 56155;56156;56157 | chr2:178600974;178600973;178600972 | chr2:179465701;179465700;179465699 |
| N2AB | 17003 | 51232;51233;51234 | chr2:178600974;178600973;178600972 | chr2:179465701;179465700;179465699 |
| N2A | 16076 | 48451;48452;48453 | chr2:178600974;178600973;178600972 | chr2:179465701;179465700;179465699 |
| N2B | 9579 | 28960;28961;28962 | chr2:178600974;178600973;178600972 | chr2:179465701;179465700;179465699 |
| Novex-1 | 9704 | 29335;29336;29337 | chr2:178600974;178600973;178600972 | chr2:179465701;179465700;179465699 |
| Novex-2 | 9771 | 29536;29537;29538 | chr2:178600974;178600973;178600972 | chr2:179465701;179465700;179465699 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/L | rs2154192554  |
None | 0.999 | N | 0.576 | 0.492 | 0.392855499163 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07555E-04 | 0 |
| F/L | rs2154192554 |
None | 0.999 | N | 0.576 | 0.492 | 0.392855499163 | gnomAD-4.0.0 | 6.578E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.07727E-04 | 0 |
| F/Y | rs879101964 |
-0.768 | 0.999 | N | 0.511 | 0.371 | None | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.49E-05 | 0 |
| F/Y | rs879101964 |
-0.768 | 0.999 | N | 0.511 | 0.371 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| F/Y | rs879101964 |
-0.768 | 0.999 | N | 0.511 | 0.371 | None | gnomAD-4.0.0 | 2.56481E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.79136E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.9406 | likely_pathogenic | 0.9248 | pathogenic | -2.709 | Highly Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | N |
| F/C | 0.6818 | likely_pathogenic | 0.6034 | pathogenic | -1.559 | Destabilizing | 1.0 | D | 0.851 | deleterious | N | 0.490198909 | None | None | N |
| F/D | 0.9856 | likely_pathogenic | 0.9823 | pathogenic | -2.977 | Highly Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | None | N |
| F/E | 0.9844 | likely_pathogenic | 0.9789 | pathogenic | -2.813 | Highly Destabilizing | 1.0 | D | 0.862 | deleterious | None | None | None | None | N |
| F/G | 0.9682 | likely_pathogenic | 0.9594 | pathogenic | -3.112 | Highly Destabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | N |
| F/H | 0.8743 | likely_pathogenic | 0.8436 | pathogenic | -1.516 | Destabilizing | 1.0 | D | 0.818 | deleterious | None | None | None | None | N |
| F/I | 0.7109 | likely_pathogenic | 0.6506 | pathogenic | -1.412 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | N | 0.519673667 | None | None | N |
| F/K | 0.985 | likely_pathogenic | 0.9809 | pathogenic | -2.038 | Highly Destabilizing | 1.0 | D | 0.868 | deleterious | None | None | None | None | N |
| F/L | 0.9712 | likely_pathogenic | 0.9561 | pathogenic | -1.412 | Destabilizing | 0.999 | D | 0.576 | neutral | N | 0.495660657 | None | None | N |
| F/M | 0.8372 | likely_pathogenic | 0.8075 | pathogenic | -0.945 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| F/N | 0.9558 | likely_pathogenic | 0.9437 | pathogenic | -2.417 | Highly Destabilizing | 1.0 | D | 0.887 | deleterious | None | None | None | None | N |
| F/P | 0.9997 | likely_pathogenic | 0.9996 | pathogenic | -1.851 | Destabilizing | 1.0 | D | 0.887 | deleterious | None | None | None | None | N |
| F/Q | 0.9735 | likely_pathogenic | 0.9635 | pathogenic | -2.441 | Highly Destabilizing | 1.0 | D | 0.889 | deleterious | None | None | None | None | N |
| F/R | 0.9683 | likely_pathogenic | 0.9588 | pathogenic | -1.409 | Destabilizing | 1.0 | D | 0.889 | deleterious | None | None | None | None | N |
| F/S | 0.9331 | likely_pathogenic | 0.9117 | pathogenic | -3.03 | Highly Destabilizing | 1.0 | D | 0.795 | deleterious | N | 0.488044689 | None | None | N |
| F/T | 0.9434 | likely_pathogenic | 0.9324 | pathogenic | -2.764 | Highly Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| F/V | 0.6821 | likely_pathogenic | 0.6214 | pathogenic | -1.851 | Destabilizing | 1.0 | D | 0.696 | prob.neutral | N | 0.499428894 | None | None | N |
| F/W | 0.7546 | likely_pathogenic | 0.737 | pathogenic | -0.553 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| F/Y | 0.1943 | likely_benign | 0.1806 | benign | -0.859 | Destabilizing | 0.999 | D | 0.511 | neutral | N | 0.465471036 | 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.