Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35913 | 107962;107963;107964 | chr2:178527251;178527250;178527249 | chr2:179391978;179391977;179391976 |
| N2AB | 34272 | 103039;103040;103041 | chr2:178527251;178527250;178527249 | chr2:179391978;179391977;179391976 |
| N2A | 33345 | 100258;100259;100260 | chr2:178527251;178527250;178527249 | chr2:179391978;179391977;179391976 |
| N2B | 26848 | 80767;80768;80769 | chr2:178527251;178527250;178527249 | chr2:179391978;179391977;179391976 |
| Novex-1 | 26973 | 81142;81143;81144 | chr2:178527251;178527250;178527249 | chr2:179391978;179391977;179391976 |
| Novex-2 | 27040 | 81343;81344;81345 | chr2:178527251;178527250;178527249 | chr2:179391978;179391977;179391976 |
| 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 | rs771568319  |
-2.45 | 0.822 | N | 0.386 | 0.129 | 0.348983352498 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | -0.696(OBSL1) -1.085(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.56E-05 | 0 |
| V/A | rs771568319 |
-2.45 | 0.822 | N | 0.386 | 0.129 | 0.348983352498 | gnomAD-4.0.0 | 6.37144E-06 | None | None | None | -0.696(OBSL1) -1.085(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.14477E-05 | 0 | 0 |
| V/F | rs1468593257 |
-1.45 | 0.032 | N | 0.238 | 0.138 | 0.43912465853 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | 0.321(OBSL1) 0.069(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| V/F | rs1468593257 |
-1.45 | 0.032 | N | 0.238 | 0.138 | 0.43912465853 | gnomAD-4.0.0 | 1.59292E-06 | None | None | None | 0.321(OBSL1) 0.069(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.862E-06 | 0 | 0 |
| V/I | None | None | 0.058 | N | 0.273 | 0.084 | 0.209622950755 | gnomAD-4.0.0 | 1.59292E-06 | None | None | None | -0.691(OBSL1) -1.06(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 2.4108E-04 | 0 | 0 | 0 |
| V/L | rs1468593257 |
None | 0.489 | N | 0.355 | 0.098 | 0.167679373172 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | -0.691(OBSL1) -1.06(OBSCN) | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/L | rs1468593257 |
None | 0.489 | N | 0.355 | 0.098 | 0.167679373172 | gnomAD-4.0.0 | 6.57056E-06 | None | None | None | -0.691(OBSL1) -1.06(OBSCN) | N | None | 2.41324E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.635 | likely_pathogenic | 0.6076 | pathogenic | -1.094 | Destabilizing | 0.822 | D | 0.386 | neutral | N | 0.45382153 | None | -0.696(OBSL1) -1.085(OBSCN) | N |
| V/C | 0.9576 | likely_pathogenic | 0.9549 | pathogenic | -0.919 | Destabilizing | 0.998 | D | 0.585 | neutral | None | None | None | -0.007(OBSL1) -0.116(OBSCN) | N |
| V/D | 0.7981 | likely_pathogenic | 0.7935 | pathogenic | -0.717 | Destabilizing | 0.99 | D | 0.745 | deleterious | N | 0.420303602 | None | -0.735(OBSL1) -1.028(OBSCN) | N |
| V/E | 0.6759 | likely_pathogenic | 0.6771 | pathogenic | -0.711 | Destabilizing | 0.993 | D | 0.705 | prob.neutral | None | None | None | -0.777(OBSL1) -1.072(OBSCN) | N |
| V/F | 0.5036 | ambiguous | 0.5132 | ambiguous | -0.744 | Destabilizing | 0.032 | N | 0.238 | neutral | N | 0.512331116 | None | 0.321(OBSL1) 0.069(OBSCN) | N |
| V/G | 0.6788 | likely_pathogenic | 0.637 | pathogenic | -1.397 | Destabilizing | 0.971 | D | 0.725 | prob.delet. | N | 0.511811041 | None | -0.716(OBSL1) -1.107(OBSCN) | N |
| V/H | 0.93 | likely_pathogenic | 0.9301 | pathogenic | -0.791 | Destabilizing | 0.998 | D | 0.722 | prob.delet. | None | None | None | -0.424(OBSL1) -0.869(OBSCN) | N |
| V/I | 0.1324 | likely_benign | 0.1478 | benign | -0.376 | Destabilizing | 0.058 | N | 0.273 | neutral | N | 0.487646102 | None | -0.691(OBSL1) -1.06(OBSCN) | N |
| V/K | 0.8276 | likely_pathogenic | 0.8049 | pathogenic | -0.996 | Destabilizing | 0.978 | D | 0.701 | prob.neutral | None | None | None | -0.987(OBSL1) -1.483(OBSCN) | N |
| V/L | 0.5841 | likely_pathogenic | 0.6165 | pathogenic | -0.376 | Destabilizing | 0.489 | N | 0.355 | neutral | N | 0.482181567 | None | -0.691(OBSL1) -1.06(OBSCN) | N |
| V/M | 0.4429 | ambiguous | 0.4601 | ambiguous | -0.436 | Destabilizing | 0.978 | D | 0.526 | neutral | None | None | None | -0.51(OBSL1) -0.609(OBSCN) | N |
| V/N | 0.7193 | likely_pathogenic | 0.7152 | pathogenic | -0.891 | Destabilizing | 0.993 | D | 0.743 | deleterious | None | None | None | 0.139(OBSL1) -0.263(OBSCN) | N |
| V/P | 0.9018 | likely_pathogenic | 0.8807 | pathogenic | -0.579 | Destabilizing | 0.993 | D | 0.705 | prob.neutral | None | None | None | -0.682(OBSL1) -1.06(OBSCN) | N |
| V/Q | 0.7928 | likely_pathogenic | 0.7842 | pathogenic | -0.998 | Destabilizing | 0.993 | D | 0.703 | prob.neutral | None | None | None | 0.025(OBSL1) -0.358(OBSCN) | N |
| V/R | 0.7917 | likely_pathogenic | 0.7629 | pathogenic | -0.511 | Destabilizing | 0.978 | D | 0.747 | deleterious | None | None | None | -1.361(OBSL1) -1.897(OBSCN) | N |
| V/S | 0.6817 | likely_pathogenic | 0.6516 | pathogenic | -1.421 | Destabilizing | 0.978 | D | 0.664 | neutral | None | None | None | 0.091(OBSL1) -0.337(OBSCN) | N |
| V/T | 0.5765 | likely_pathogenic | 0.5628 | ambiguous | -1.293 | Destabilizing | 0.926 | D | 0.427 | neutral | None | None | None | 0.031(OBSL1) -0.397(OBSCN) | N |
| V/W | 0.9712 | likely_pathogenic | 0.9706 | pathogenic | -0.921 | Destabilizing | 0.998 | D | 0.745 | deleterious | None | None | None | 0.146(OBSL1) 0.008(OBSCN) | N |
| V/Y | 0.8578 | likely_pathogenic | 0.8567 | pathogenic | -0.615 | Destabilizing | 0.915 | D | 0.579 | neutral | None | None | None | 0.382(OBSL1) 0.156(OBSCN) | 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.