Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17154 | 51685;51686;51687 | chr2:178609963;178609962;178609961 | chr2:179474690;179474689;179474688 |
| N2AB | 15513 | 46762;46763;46764 | chr2:178609963;178609962;178609961 | chr2:179474690;179474689;179474688 |
| N2A | 14586 | 43981;43982;43983 | chr2:178609963;178609962;178609961 | chr2:179474690;179474689;179474688 |
| N2B | 8089 | 24490;24491;24492 | chr2:178609963;178609962;178609961 | chr2:179474690;179474689;179474688 |
| Novex-1 | 8214 | 24865;24866;24867 | chr2:178609963;178609962;178609961 | chr2:179474690;179474689;179474688 |
| Novex-2 | 8281 | 25066;25067;25068 | chr2:178609963;178609962;178609961 | chr2:179474690;179474689;179474688 |
| 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 | rs371799925  |
-2.473 | 0.822 | N | 0.685 | 0.272 | None | gnomAD-2.1.1 | 2.15E-05 | None | None | None | None | N | None | 2.48242E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/A | rs371799925 |
-2.473 | 0.822 | N | 0.685 | 0.272 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 1.2072E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/A | rs371799925 |
-2.473 | 0.822 | N | 0.685 | 0.272 | None | gnomAD-4.0.0 | 4.34174E-06 | None | None | None | None | N | None | 9.35929E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs374701373 |
-0.765 | 0.489 | N | 0.618 | 0.059 | None | gnomAD-2.1.1 | 2.02E-05 | None | None | None | None | N | None | 1.94099E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.79E-05 | 0 |
| V/I | rs374701373 |
-0.765 | 0.489 | N | 0.618 | 0.059 | None | gnomAD-3.1.2 | 4.61E-05 | None | None | None | None | N | None | 1.20726E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| V/I | rs374701373 |
-0.765 | 0.489 | N | 0.618 | 0.059 | None | gnomAD-4.0.0 | 9.30448E-06 | None | None | None | None | N | None | 9.36054E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 6.78541E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.8136 | likely_pathogenic | 0.7275 | pathogenic | -1.759 | Destabilizing | 0.822 | D | 0.685 | prob.neutral | N | 0.506691301 | None | None | N |
| V/C | 0.9495 | likely_pathogenic | 0.9335 | pathogenic | -1.648 | Destabilizing | 0.998 | D | 0.679 | prob.neutral | None | None | None | None | N |
| V/D | 0.9972 | likely_pathogenic | 0.9945 | pathogenic | -2.301 | Highly Destabilizing | 0.993 | D | 0.805 | deleterious | None | None | None | None | N |
| V/E | 0.9925 | likely_pathogenic | 0.9868 | pathogenic | -2.232 | Highly Destabilizing | 0.971 | D | 0.767 | deleterious | N | 0.510445039 | None | None | N |
| V/F | 0.9362 | likely_pathogenic | 0.8841 | pathogenic | -1.341 | Destabilizing | 0.915 | D | 0.734 | prob.delet. | None | None | None | None | N |
| V/G | 0.922 | likely_pathogenic | 0.883 | pathogenic | -2.136 | Highly Destabilizing | 0.971 | D | 0.813 | deleterious | N | 0.500191597 | None | None | N |
| V/H | 0.9985 | likely_pathogenic | 0.9971 | pathogenic | -1.778 | Destabilizing | 0.998 | D | 0.767 | deleterious | None | None | None | None | N |
| V/I | 0.1302 | likely_benign | 0.1248 | benign | -0.779 | Destabilizing | 0.489 | N | 0.618 | neutral | N | 0.457262559 | None | None | N |
| V/K | 0.9937 | likely_pathogenic | 0.9889 | pathogenic | -1.407 | Destabilizing | 0.978 | D | 0.769 | deleterious | None | None | None | None | N |
| V/L | 0.4958 | ambiguous | 0.4682 | ambiguous | -0.779 | Destabilizing | 0.006 | N | 0.292 | neutral | N | 0.40936425 | None | None | N |
| V/M | 0.6958 | likely_pathogenic | 0.6022 | pathogenic | -0.878 | Destabilizing | 0.956 | D | 0.716 | prob.delet. | None | None | None | None | N |
| V/N | 0.9892 | likely_pathogenic | 0.981 | pathogenic | -1.449 | Destabilizing | 0.993 | D | 0.817 | deleterious | None | None | None | None | N |
| V/P | 0.939 | likely_pathogenic | 0.8998 | pathogenic | -1.074 | Destabilizing | 0.993 | D | 0.753 | deleterious | None | None | None | None | N |
| V/Q | 0.9927 | likely_pathogenic | 0.9868 | pathogenic | -1.563 | Destabilizing | 0.993 | D | 0.767 | deleterious | None | None | None | None | N |
| V/R | 0.9895 | likely_pathogenic | 0.9825 | pathogenic | -1.039 | Destabilizing | 0.978 | D | 0.809 | deleterious | None | None | None | None | N |
| V/S | 0.9664 | likely_pathogenic | 0.9406 | pathogenic | -1.973 | Destabilizing | 0.978 | D | 0.769 | deleterious | None | None | None | None | N |
| V/T | 0.7899 | likely_pathogenic | 0.7047 | pathogenic | -1.787 | Destabilizing | 0.86 | D | 0.713 | prob.delet. | None | None | None | None | N |
| V/W | 0.9987 | likely_pathogenic | 0.9972 | pathogenic | -1.634 | Destabilizing | 0.998 | D | 0.758 | deleterious | None | None | None | None | N |
| V/Y | 0.9959 | likely_pathogenic | 0.9915 | pathogenic | -1.287 | Destabilizing | 0.978 | D | 0.713 | 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.