Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23622 | 71089;71090;71091 | chr2:178575268;178575267;178575266 | chr2:179439995;179439994;179439993 |
| N2AB | 21981 | 66166;66167;66168 | chr2:178575268;178575267;178575266 | chr2:179439995;179439994;179439993 |
| N2A | 21054 | 63385;63386;63387 | chr2:178575268;178575267;178575266 | chr2:179439995;179439994;179439993 |
| N2B | 14557 | 43894;43895;43896 | chr2:178575268;178575267;178575266 | chr2:179439995;179439994;179439993 |
| Novex-1 | 14682 | 44269;44270;44271 | chr2:178575268;178575267;178575266 | chr2:179439995;179439994;179439993 |
| Novex-2 | 14749 | 44470;44471;44472 | chr2:178575268;178575267;178575266 | chr2:179439995;179439994;179439993 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | None | None | 0.014 | N | 0.293 | 0.208 | 0.331876078066 | gnomAD-4.0.0 | 3.18454E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8595E-06 | 1.43291E-05 | 0 |
| V/I | rs72646892  |
-0.066 | 0.007 | N | 0.294 | 0.045 | None | gnomAD-2.1.1 | 4.03E-05 | None | None | None | None | N | None | 0 | 2.91E-05 | None | 0 | 0 | None | 0 | None | 0 | 8.02E-05 | 0 |
| V/I | rs72646892 |
-0.066 | 0.007 | N | 0.294 | 0.045 | None | gnomAD-3.1.2 | 8.55E-05 | None | None | None | None | N | None | 0 | 0 | 5.48246E-03 | 0 | 1.93723E-04 | None | 0 | 0 | 1.02974E-04 | 0 | 0 |
| V/I | rs72646892 |
-0.066 | 0.007 | N | 0.294 | 0.045 | None | gnomAD-4.0.0 | 4.09147E-05 | None | None | None | None | N | None | 1.33533E-05 | 1.66778E-05 | None | 0 | 4.47989E-05 | None | 0 | 0 | 4.40845E-05 | 2.1964E-05 | 4.80538E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.4938 | ambiguous | 0.5082 | ambiguous | -1.606 | Destabilizing | 0.014 | N | 0.293 | neutral | N | 0.502889579 | None | None | N |
| V/C | 0.8642 | likely_pathogenic | 0.8828 | pathogenic | -1.049 | Destabilizing | 0.996 | D | 0.619 | neutral | None | None | None | None | N |
| V/D | 0.9631 | likely_pathogenic | 0.9622 | pathogenic | -2.014 | Highly Destabilizing | 0.978 | D | 0.759 | deleterious | N | 0.487738293 | None | None | N |
| V/E | 0.8878 | likely_pathogenic | 0.8914 | pathogenic | -1.763 | Destabilizing | 0.906 | D | 0.671 | prob.neutral | None | None | None | None | N |
| V/F | 0.4407 | ambiguous | 0.4288 | ambiguous | -0.875 | Destabilizing | 0.977 | D | 0.72 | deleterious | N | 0.474363617 | None | None | N |
| V/G | 0.7354 | likely_pathogenic | 0.7465 | pathogenic | -2.157 | Highly Destabilizing | 0.896 | D | 0.67 | prob.neutral | N | 0.505170985 | None | None | N |
| V/H | 0.9447 | likely_pathogenic | 0.9497 | pathogenic | -1.895 | Destabilizing | 0.997 | D | 0.72 | deleterious | None | None | None | None | N |
| V/I | 0.0947 | likely_benign | 0.0915 | benign | -0.069 | Destabilizing | 0.007 | N | 0.294 | neutral | N | 0.484384871 | None | None | N |
| V/K | 0.9121 | likely_pathogenic | 0.9176 | pathogenic | -1.297 | Destabilizing | 0.955 | D | 0.671 | prob.neutral | None | None | None | None | N |
| V/L | 0.4225 | ambiguous | 0.4059 | ambiguous | -0.069 | Destabilizing | 0.068 | N | 0.565 | neutral | N | 0.515457139 | None | None | N |
| V/M | 0.3073 | likely_benign | 0.2978 | benign | -0.139 | Destabilizing | 0.941 | D | 0.607 | neutral | None | None | None | None | N |
| V/N | 0.8888 | likely_pathogenic | 0.8919 | pathogenic | -1.722 | Destabilizing | 0.759 | D | 0.769 | deleterious | None | None | None | None | N |
| V/P | 0.9836 | likely_pathogenic | 0.983 | pathogenic | -0.554 | Destabilizing | 0.759 | D | 0.675 | prob.neutral | None | None | None | None | N |
| V/Q | 0.8511 | likely_pathogenic | 0.8589 | pathogenic | -1.48 | Destabilizing | 0.979 | D | 0.689 | prob.delet. | None | None | None | None | N |
| V/R | 0.8821 | likely_pathogenic | 0.8838 | pathogenic | -1.315 | Destabilizing | 0.978 | D | 0.773 | deleterious | None | None | None | None | N |
| V/S | 0.7459 | likely_pathogenic | 0.7618 | pathogenic | -2.342 | Highly Destabilizing | 0.632 | D | 0.609 | neutral | None | None | None | None | N |
| V/T | 0.514 | ambiguous | 0.5607 | ambiguous | -1.929 | Destabilizing | 0.018 | N | 0.346 | neutral | None | None | None | None | N |
| V/W | 0.9754 | likely_pathogenic | 0.9758 | pathogenic | -1.382 | Destabilizing | 0.999 | D | 0.752 | deleterious | None | None | None | None | N |
| V/Y | 0.8855 | likely_pathogenic | 0.8851 | pathogenic | -0.915 | Destabilizing | 0.978 | D | 0.7 | 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.