Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 5060 | 15403;15404;15405 | chr2:178734746;178734745;178734744 | chr2:179599473;179599472;179599471 |
| N2AB | 4743 | 14452;14453;14454 | chr2:178734746;178734745;178734744 | chr2:179599473;179599472;179599471 |
| N2A | 3816 | 11671;11672;11673 | chr2:178734746;178734745;178734744 | chr2:179599473;179599472;179599471 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/I | rs72648929  |
-0.015 | 0.915 | N | 0.379 | 0.208 | None | gnomAD-2.1.1 | 2.50423E-03 | None | None | None | None | I | None | 0 | 0 | None | 0 | 3.43785E-02 | None | 2.61883E-04 | None | 0 | 8.6E-05 | 1.54712E-03 |
| V/I | rs72648929 |
-0.015 | 0.915 | N | 0.379 | 0.208 | None | gnomAD-3.1.2 | 9.66101E-04 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 2.58189E-02 | None | 0 | 0 | 8.82E-05 | 8.28157E-04 | 9.56023E-04 |
| V/I | rs72648929 |
-0.015 | 0.915 | N | 0.379 | 0.208 | None | 1000 genomes | 4.39297E-03 | None | None | None | None | I | None | 0 | 0 | None | None | 2.08E-02 | 1E-03 | None | None | None | 0 | None |
| V/I | rs72648929 |
-0.015 | 0.915 | N | 0.379 | 0.208 | None | gnomAD-4.0.0 | 9.22373E-04 | None | None | None | None | I | None | 1.33269E-05 | 0 | None | 0 | 2.89803E-02 | None | 0 | 1.6518E-04 | 5.85098E-05 | 2.96606E-04 | 1.44069E-03 |
| V/L | rs72648929 |
-0.002 | 0.708 | N | 0.386 | 0.236 | None | gnomAD-2.1.1 | 3.20085E-03 | None | None | None | None | I | None | 1.65385E-04 | 6.50784E-04 | None | 8.80929E-03 | 0 | None | 7.82375E-03 | None | 1.60334E-03 | 3.72819E-03 | 3.09423E-03 |
| V/L | rs72648929 |
-0.002 | 0.708 | N | 0.386 | 0.236 | None | gnomAD-3.1.2 | 2.35282E-03 | None | None | None | None | I | None | 4.34174E-04 | 5.89623E-04 | 0 | 9.51009E-03 | 3.85356E-04 | None | 1.88395E-03 | 0 | 3.35245E-03 | 8.90269E-03 | 2.39006E-03 |
| V/L | rs72648929 |
-0.002 | 0.708 | N | 0.386 | 0.236 | None | 1000 genomes | 3.39457E-03 | None | None | None | None | I | None | 0 | 1.4E-03 | None | None | 0 | 4E-03 | None | None | None | 1.23E-02 | None |
| V/L | rs72648929 |
-0.002 | 0.708 | N | 0.386 | 0.236 | None | gnomAD-4.0.0 | 3.17871E-03 | None | None | None | None | I | None | 4.66443E-04 | 6.66756E-04 | None | 9.69791E-03 | 1.56048E-04 | None | 1.40638E-03 | 9.41526E-03 | 3.08998E-03 | 8.45875E-03 | 3.16952E-03 |
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 | 0.102 | likely_benign | 0.1221 | benign | -0.371 | Destabilizing | 0.002 | N | 0.257 | neutral | N | 0.381480216 | None | None | I |
| V/C | 0.764 | likely_pathogenic | 0.8146 | pathogenic | -0.831 | Destabilizing | 0.994 | D | 0.507 | neutral | None | None | None | None | I |
| V/D | 0.6074 | likely_pathogenic | 0.6641 | pathogenic | -0.42 | Destabilizing | 0.97 | D | 0.607 | neutral | D | 0.558775783 | None | None | I |
| V/E | 0.5118 | ambiguous | 0.5621 | ambiguous | -0.541 | Destabilizing | 0.956 | D | 0.525 | neutral | None | None | None | None | I |
| V/F | 0.2322 | likely_benign | 0.2517 | benign | -0.795 | Destabilizing | 0.988 | D | 0.483 | neutral | N | 0.509080442 | None | None | I |
| V/G | 0.3156 | likely_benign | 0.3799 | ambiguous | -0.409 | Destabilizing | 0.698 | D | 0.518 | neutral | N | 0.513733604 | None | None | I |
| V/H | 0.7618 | likely_pathogenic | 0.8079 | pathogenic | -0.035 | Destabilizing | 0.998 | D | 0.633 | neutral | None | None | None | None | I |
| V/I | 0.0902 | likely_benign | 0.0889 | benign | -0.409 | Destabilizing | 0.915 | D | 0.379 | neutral | N | 0.500166664 | None | None | I |
| V/K | 0.696 | likely_pathogenic | 0.7302 | pathogenic | -0.4 | Destabilizing | 0.956 | D | 0.533 | neutral | None | None | None | None | I |
| V/L | 0.3489 | ambiguous | 0.3951 | ambiguous | -0.409 | Destabilizing | 0.708 | D | 0.386 | neutral | N | 0.48486702 | None | None | I |
| V/M | 0.1826 | likely_benign | 0.2119 | benign | -0.602 | Destabilizing | 0.993 | D | 0.423 | neutral | None | None | None | None | I |
| V/N | 0.4775 | ambiguous | 0.5527 | ambiguous | -0.201 | Destabilizing | 0.978 | D | 0.623 | neutral | None | None | None | None | I |
| V/P | 0.9143 | likely_pathogenic | 0.9454 | pathogenic | -0.371 | Destabilizing | 0.978 | D | 0.577 | neutral | None | None | None | None | I |
| V/Q | 0.5879 | likely_pathogenic | 0.6383 | pathogenic | -0.424 | Destabilizing | 0.978 | D | 0.605 | neutral | None | None | None | None | I |
| V/R | 0.5979 | likely_pathogenic | 0.632 | pathogenic | 0.051 | Stabilizing | 0.978 | D | 0.618 | neutral | None | None | None | None | I |
| V/S | 0.2103 | likely_benign | 0.2652 | benign | -0.499 | Destabilizing | 0.754 | D | 0.511 | neutral | None | None | None | None | I |
| V/T | 0.1659 | likely_benign | 0.2014 | benign | -0.534 | Destabilizing | 0.86 | D | 0.342 | neutral | None | None | None | None | I |
| V/W | 0.8825 | likely_pathogenic | 0.9039 | pathogenic | -0.835 | Destabilizing | 0.998 | D | 0.673 | neutral | None | None | None | None | I |
| V/Y | 0.6817 | likely_pathogenic | 0.7263 | pathogenic | -0.573 | Destabilizing | 0.993 | D | 0.478 | neutral | None | None | None | None | I |
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.