Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19653 | 59182;59183;59184 | chr2:178593251;178593250;178593249 | chr2:179457978;179457977;179457976 |
| N2AB | 18012 | 54259;54260;54261 | chr2:178593251;178593250;178593249 | chr2:179457978;179457977;179457976 |
| N2A | 17085 | 51478;51479;51480 | chr2:178593251;178593250;178593249 | chr2:179457978;179457977;179457976 |
| N2B | 10588 | 31987;31988;31989 | chr2:178593251;178593250;178593249 | chr2:179457978;179457977;179457976 |
| Novex-1 | 10713 | 32362;32363;32364 | chr2:178593251;178593250;178593249 | chr2:179457978;179457977;179457976 |
| Novex-2 | 10780 | 32563;32564;32565 | chr2:178593251;178593250;178593249 | chr2:179457978;179457977;179457976 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/Q | rs1398360418  |
-1.162 | 1.0 | N | 0.777 | 0.471 | 0.368554958709 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| R/Q | rs1398360418 |
-1.162 | 1.0 | N | 0.777 | 0.471 | 0.368554958709 | 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 |
| R/Q | rs1398360418 |
-1.162 | 1.0 | N | 0.777 | 0.471 | 0.368554958709 | gnomAD-4.0.0 | 7.69136E-06 | None | None | None | None | N | None | 0 | 1.69641E-05 | None | 0 | 0 | None | 0 | 0 | 4.78824E-06 | 4.02209E-05 | 0 |
| R/W | rs149325705 |
-0.911 | 1.0 | D | 0.829 | 0.672 | None | gnomAD-2.1.1 | 2.42E-05 | None | None | None | None | N | None | 6.46E-05 | 8.71E-05 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 8.9E-06 | 0 |
| R/W | rs149325705 |
-0.911 | 1.0 | D | 0.829 | 0.672 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 2.41E-05 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/W | rs149325705 |
-0.911 | 1.0 | D | 0.829 | 0.672 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/W | rs149325705 |
-0.911 | 1.0 | D | 0.829 | 0.672 | None | gnomAD-4.0.0 | 1.36363E-05 | None | None | None | None | N | None | 2.66724E-05 | 6.67111E-05 | None | 3.38043E-05 | 0 | None | 0 | 0 | 1.10209E-05 | 2.19645E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9694 | likely_pathogenic | 0.9651 | pathogenic | -2.03 | Highly Destabilizing | 0.999 | D | 0.649 | neutral | None | None | None | None | N |
| R/C | 0.5641 | likely_pathogenic | 0.537 | ambiguous | -1.907 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| R/D | 0.9973 | likely_pathogenic | 0.9975 | pathogenic | -1.017 | Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | N |
| R/E | 0.9488 | likely_pathogenic | 0.9513 | pathogenic | -0.794 | Destabilizing | 0.999 | D | 0.665 | neutral | None | None | None | None | N |
| R/F | 0.9689 | likely_pathogenic | 0.9724 | pathogenic | -1.215 | Destabilizing | 1.0 | D | 0.875 | deleterious | None | None | None | None | N |
| R/G | 0.9778 | likely_pathogenic | 0.9761 | pathogenic | -2.373 | Highly Destabilizing | 1.0 | D | 0.765 | deleterious | D | 0.560732106 | None | None | N |
| R/H | 0.3185 | likely_benign | 0.3657 | ambiguous | -2.155 | Highly Destabilizing | 1.0 | D | 0.812 | deleterious | None | None | None | None | N |
| R/I | 0.9059 | likely_pathogenic | 0.8983 | pathogenic | -1.029 | Destabilizing | 1.0 | D | 0.862 | deleterious | None | None | None | None | N |
| R/K | 0.4917 | ambiguous | 0.4442 | ambiguous | -1.261 | Destabilizing | 0.998 | D | 0.667 | neutral | None | None | None | None | N |
| R/L | 0.8752 | likely_pathogenic | 0.8757 | pathogenic | -1.029 | Destabilizing | 1.0 | D | 0.765 | deleterious | N | 0.521485403 | None | None | N |
| R/M | 0.9223 | likely_pathogenic | 0.9143 | pathogenic | -1.562 | Destabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | N |
| R/N | 0.9883 | likely_pathogenic | 0.9891 | pathogenic | -1.328 | Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| R/P | 0.999 | likely_pathogenic | 0.999 | pathogenic | -1.353 | Destabilizing | 1.0 | D | 0.83 | deleterious | D | 0.561239085 | None | None | N |
| R/Q | 0.3672 | ambiguous | 0.3645 | ambiguous | -1.173 | Destabilizing | 1.0 | D | 0.777 | deleterious | N | 0.505708098 | None | None | N |
| R/S | 0.9818 | likely_pathogenic | 0.9796 | pathogenic | -2.217 | Highly Destabilizing | 1.0 | D | 0.744 | deleterious | None | None | None | None | N |
| R/T | 0.9612 | likely_pathogenic | 0.956 | pathogenic | -1.78 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| R/V | 0.9238 | likely_pathogenic | 0.9192 | pathogenic | -1.353 | Destabilizing | 1.0 | D | 0.832 | deleterious | None | None | None | None | N |
| R/W | 0.7131 | likely_pathogenic | 0.7287 | pathogenic | -0.732 | Destabilizing | 1.0 | D | 0.829 | deleterious | D | 0.549464706 | None | None | N |
| R/Y | 0.9265 | likely_pathogenic | 0.9315 | pathogenic | -0.604 | Destabilizing | 1.0 | D | 0.867 | deleterious | 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.