Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 9360 | 28303;28304;28305 | chr2:178711158;178711157;178711156 | chr2:179575885;179575884;179575883 |
| N2AB | 9043 | 27352;27353;27354 | chr2:178711158;178711157;178711156 | chr2:179575885;179575884;179575883 |
| N2A | 8116 | 24571;24572;24573 | chr2:178711158;178711157;178711156 | chr2:179575885;179575884;179575883 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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/S | rs745880964  |
-3.646 | 1.0 | None | 0.883 | 0.887 | 0.936186774989 | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | N | None | 0 | 1.13122E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/S | rs745880964 |
-3.646 | 1.0 | None | 0.883 | 0.887 | 0.936186774989 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/S | rs745880964 |
-3.646 | 1.0 | None | 0.883 | 0.887 | 0.936186774989 | gnomAD-4.0.0 | 6.40467E-06 | None | None | None | None | N | None | 0 | 8.47285E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs2076598524 |
None | 0.993 | None | 0.389 | 0.473 | 0.771852621965 | gnomAD-4.0.0 | 6.84185E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99457E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9027 | likely_pathogenic | 0.9236 | pathogenic | -2.992 | Highly Destabilizing | 0.999 | D | 0.733 | prob.delet. | None | None | None | None | N |
| I/C | 0.8956 | likely_pathogenic | 0.9135 | pathogenic | -2.206 | Highly Destabilizing | 1.0 | D | 0.846 | deleterious | None | None | None | None | N |
| I/D | 0.9898 | likely_pathogenic | 0.9938 | pathogenic | -3.659 | Highly Destabilizing | 1.0 | D | 0.895 | deleterious | None | None | None | None | N |
| I/E | 0.9886 | likely_pathogenic | 0.9922 | pathogenic | -3.365 | Highly Destabilizing | 1.0 | D | 0.897 | deleterious | None | None | None | None | N |
| I/F | 0.2004 | likely_benign | 0.2403 | benign | -1.806 | Destabilizing | 1.0 | D | 0.842 | deleterious | None | None | None | None | N |
| I/G | 0.9772 | likely_pathogenic | 0.9848 | pathogenic | -3.586 | Highly Destabilizing | 1.0 | D | 0.896 | deleterious | None | None | None | None | N |
| I/H | 0.9276 | likely_pathogenic | 0.9486 | pathogenic | -3.175 | Highly Destabilizing | 1.0 | D | 0.896 | deleterious | None | None | None | None | N |
| I/K | 0.9763 | likely_pathogenic | 0.9833 | pathogenic | -2.469 | Highly Destabilizing | 1.0 | D | 0.896 | deleterious | None | None | None | None | N |
| I/L | 0.1625 | likely_benign | 0.166 | benign | -1.22 | Destabilizing | 0.993 | D | 0.411 | neutral | None | None | None | None | N |
| I/M | 0.2773 | likely_benign | 0.2778 | benign | -1.235 | Destabilizing | 1.0 | D | 0.786 | deleterious | None | None | None | None | N |
| I/N | 0.8871 | likely_pathogenic | 0.9169 | pathogenic | -3.056 | Highly Destabilizing | 1.0 | D | 0.907 | deleterious | None | None | None | None | N |
| I/P | 0.9915 | likely_pathogenic | 0.9954 | pathogenic | -1.8 | Destabilizing | 1.0 | D | 0.903 | deleterious | None | None | None | None | N |
| I/Q | 0.9693 | likely_pathogenic | 0.9788 | pathogenic | -2.781 | Highly Destabilizing | 1.0 | D | 0.915 | deleterious | None | None | None | None | N |
| I/R | 0.9464 | likely_pathogenic | 0.9618 | pathogenic | -2.283 | Highly Destabilizing | 1.0 | D | 0.902 | deleterious | None | None | None | None | N |
| I/S | 0.9014 | likely_pathogenic | 0.9241 | pathogenic | -3.671 | Highly Destabilizing | 1.0 | D | 0.883 | deleterious | None | None | None | None | N |
| I/T | 0.9245 | likely_pathogenic | 0.9325 | pathogenic | -3.226 | Highly Destabilizing | 1.0 | D | 0.849 | deleterious | None | None | None | None | N |
| I/V | 0.1502 | likely_benign | 0.1542 | benign | -1.8 | Destabilizing | 0.993 | D | 0.389 | neutral | None | None | None | None | N |
| I/W | 0.9235 | likely_pathogenic | 0.949 | pathogenic | -2.297 | Highly Destabilizing | 1.0 | D | 0.887 | deleterious | None | None | None | None | N |
| I/Y | 0.6827 | likely_pathogenic | 0.7532 | pathogenic | -2.064 | Highly Destabilizing | 1.0 | D | 0.855 | 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.