Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23569 | 70930;70931;70932 | chr2:178575427;178575426;178575425 | chr2:179440154;179440153;179440152 |
| N2AB | 21928 | 66007;66008;66009 | chr2:178575427;178575426;178575425 | chr2:179440154;179440153;179440152 |
| N2A | 21001 | 63226;63227;63228 | chr2:178575427;178575426;178575425 | chr2:179440154;179440153;179440152 |
| N2B | 14504 | 43735;43736;43737 | chr2:178575427;178575426;178575425 | chr2:179440154;179440153;179440152 |
| Novex-1 | 14629 | 44110;44111;44112 | chr2:178575427;178575426;178575425 | chr2:179440154;179440153;179440152 |
| Novex-2 | 14696 | 44311;44312;44313 | chr2:178575427;178575426;178575425 | chr2:179440154;179440153;179440152 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs1395180090  |
None | 0.822 | D | 0.62 | 0.45 | 0.79435206604 | gnomAD-4.0.0 | 2.73717E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.87266E-05 | 0 | 8.9957E-07 | 0 | 3.31356E-05 |
| I/V | rs1283599647 |
-1.936 | 0.014 | N | 0.233 | 0.068 | 0.283371740733 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 1.14784E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs1283599647 |
-1.936 | 0.014 | N | 0.233 | 0.068 | 0.283371740733 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 4.82E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs1283599647 |
-1.936 | 0.014 | N | 0.233 | 0.068 | 0.283371740733 | gnomAD-4.0.0 | 1.31451E-05 | None | None | None | None | N | None | 4.82439E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.7716 | likely_pathogenic | 0.7799 | pathogenic | -3.099 | Highly Destabilizing | 0.754 | D | 0.625 | neutral | None | None | None | None | N |
| I/C | 0.9482 | likely_pathogenic | 0.9548 | pathogenic | -2.309 | Highly Destabilizing | 0.998 | D | 0.749 | deleterious | None | None | None | None | N |
| I/D | 0.9991 | likely_pathogenic | 0.999 | pathogenic | -3.791 | Highly Destabilizing | 0.993 | D | 0.876 | deleterious | None | None | None | None | N |
| I/E | 0.9955 | likely_pathogenic | 0.995 | pathogenic | -3.487 | Highly Destabilizing | 0.978 | D | 0.869 | deleterious | None | None | None | None | N |
| I/F | 0.7316 | likely_pathogenic | 0.7273 | pathogenic | -1.759 | Destabilizing | 0.942 | D | 0.634 | neutral | D | 0.533329596 | None | None | N |
| I/G | 0.989 | likely_pathogenic | 0.9888 | pathogenic | -3.673 | Highly Destabilizing | 0.978 | D | 0.861 | deleterious | None | None | None | None | N |
| I/H | 0.9961 | likely_pathogenic | 0.9961 | pathogenic | -3.208 | Highly Destabilizing | 0.998 | D | 0.864 | deleterious | None | None | None | None | N |
| I/K | 0.9918 | likely_pathogenic | 0.9914 | pathogenic | -2.458 | Highly Destabilizing | 0.978 | D | 0.869 | deleterious | None | None | None | None | N |
| I/L | 0.1599 | likely_benign | 0.177 | benign | -1.359 | Destabilizing | 0.006 | N | 0.299 | neutral | N | 0.501688126 | None | None | N |
| I/M | 0.2398 | likely_benign | 0.253 | benign | -1.528 | Destabilizing | 0.942 | D | 0.619 | neutral | N | 0.483700866 | None | None | N |
| I/N | 0.9903 | likely_pathogenic | 0.9894 | pathogenic | -3.117 | Highly Destabilizing | 0.99 | D | 0.885 | deleterious | D | 0.533583086 | None | None | N |
| I/P | 0.9928 | likely_pathogenic | 0.9922 | pathogenic | -1.933 | Destabilizing | 0.993 | D | 0.881 | deleterious | None | None | None | None | N |
| I/Q | 0.9918 | likely_pathogenic | 0.9913 | pathogenic | -2.81 | Highly Destabilizing | 0.993 | D | 0.891 | deleterious | None | None | None | None | N |
| I/R | 0.9869 | likely_pathogenic | 0.9858 | pathogenic | -2.332 | Highly Destabilizing | 0.978 | D | 0.882 | deleterious | None | None | None | None | N |
| I/S | 0.9616 | likely_pathogenic | 0.9599 | pathogenic | -3.664 | Highly Destabilizing | 0.97 | D | 0.776 | deleterious | D | 0.533583086 | None | None | N |
| I/T | 0.672 | likely_pathogenic | 0.6684 | pathogenic | -3.217 | Highly Destabilizing | 0.822 | D | 0.62 | neutral | D | 0.533329596 | None | None | N |
| I/V | 0.0908 | likely_benign | 0.0979 | benign | -1.933 | Destabilizing | 0.014 | N | 0.233 | neutral | N | 0.387258182 | None | None | N |
| I/W | 0.9924 | likely_pathogenic | 0.9923 | pathogenic | -2.194 | Highly Destabilizing | 0.998 | D | 0.836 | deleterious | None | None | None | None | N |
| I/Y | 0.9831 | likely_pathogenic | 0.9823 | pathogenic | -2.06 | Highly Destabilizing | 0.978 | D | 0.739 | prob.delet. | 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.