Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27699 | 83320;83321;83322 | chr2:178563037;178563036;178563035 | chr2:179427764;179427763;179427762 |
| N2AB | 26058 | 78397;78398;78399 | chr2:178563037;178563036;178563035 | chr2:179427764;179427763;179427762 |
| N2A | 25131 | 75616;75617;75618 | chr2:178563037;178563036;178563035 | chr2:179427764;179427763;179427762 |
| N2B | 18634 | 56125;56126;56127 | chr2:178563037;178563036;178563035 | chr2:179427764;179427763;179427762 |
| Novex-1 | 18759 | 56500;56501;56502 | chr2:178563037;178563036;178563035 | chr2:179427764;179427763;179427762 |
| Novex-2 | 18826 | 56701;56702;56703 | chr2:178563037;178563036;178563035 | chr2:179427764;179427763;179427762 |
| 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/N | None | None | 0.994 | D | 0.806 | 0.643 | 0.899465142518 | gnomAD-4.0.0 | 6.84242E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9952E-07 | 0 | 0 |
| I/T | rs1411163896  |
-2.383 | 0.892 | N | 0.726 | 0.553 | 0.760912148185 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs1411163896 |
-2.383 | 0.892 | N | 0.726 | 0.553 | 0.760912148185 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs1411163896 |
-2.383 | 0.892 | N | 0.726 | 0.553 | 0.760912148185 | gnomAD-4.0.0 | 1.85927E-06 | None | None | None | None | N | None | 4.00598E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | None | None | 0.011 | N | 0.201 | 0.154 | 0.443592365053 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 | 0.9171 | likely_pathogenic | 0.8955 | pathogenic | -1.952 | Destabilizing | 0.845 | D | 0.643 | neutral | None | None | None | None | N |
| I/C | 0.9285 | likely_pathogenic | 0.9224 | pathogenic | -1.464 | Destabilizing | 0.999 | D | 0.753 | deleterious | None | None | None | None | N |
| I/D | 0.9991 | likely_pathogenic | 0.9986 | pathogenic | -1.082 | Destabilizing | 0.996 | D | 0.813 | deleterious | None | None | None | None | N |
| I/E | 0.9958 | likely_pathogenic | 0.9943 | pathogenic | -0.996 | Destabilizing | 0.987 | D | 0.812 | deleterious | None | None | None | None | N |
| I/F | 0.3744 | ambiguous | 0.3666 | ambiguous | -1.238 | Destabilizing | 0.967 | D | 0.747 | deleterious | N | 0.489311554 | None | None | N |
| I/G | 0.9896 | likely_pathogenic | 0.9867 | pathogenic | -2.37 | Highly Destabilizing | 0.987 | D | 0.81 | deleterious | None | None | None | None | N |
| I/H | 0.983 | likely_pathogenic | 0.9796 | pathogenic | -1.559 | Destabilizing | 0.999 | D | 0.788 | deleterious | None | None | None | None | N |
| I/K | 0.9794 | likely_pathogenic | 0.9707 | pathogenic | -1.294 | Destabilizing | 0.987 | D | 0.812 | deleterious | None | None | None | None | N |
| I/L | 0.3179 | likely_benign | 0.284 | benign | -0.835 | Destabilizing | 0.426 | N | 0.422 | neutral | N | 0.499827928 | None | None | N |
| I/M | 0.2952 | likely_benign | 0.2609 | benign | -0.802 | Destabilizing | 0.983 | D | 0.717 | prob.delet. | N | 0.509742656 | None | None | N |
| I/N | 0.9799 | likely_pathogenic | 0.9703 | pathogenic | -1.249 | Destabilizing | 0.994 | D | 0.806 | deleterious | D | 0.539710195 | None | None | N |
| I/P | 0.9932 | likely_pathogenic | 0.9919 | pathogenic | -1.178 | Destabilizing | 0.996 | D | 0.801 | deleterious | None | None | None | None | N |
| I/Q | 0.9837 | likely_pathogenic | 0.9789 | pathogenic | -1.296 | Destabilizing | 0.996 | D | 0.807 | deleterious | None | None | None | None | N |
| I/R | 0.9664 | likely_pathogenic | 0.9531 | pathogenic | -0.855 | Destabilizing | 0.987 | D | 0.813 | deleterious | None | None | None | None | N |
| I/S | 0.9535 | likely_pathogenic | 0.9381 | pathogenic | -2.043 | Highly Destabilizing | 0.983 | D | 0.787 | deleterious | N | 0.505223205 | None | None | N |
| I/T | 0.9272 | likely_pathogenic | 0.9079 | pathogenic | -1.815 | Destabilizing | 0.892 | D | 0.726 | prob.delet. | N | 0.500081417 | None | None | N |
| I/V | 0.1212 | likely_benign | 0.122 | benign | -1.178 | Destabilizing | 0.011 | N | 0.201 | neutral | N | 0.432713618 | None | None | N |
| I/W | 0.97 | likely_pathogenic | 0.9691 | pathogenic | -1.333 | Destabilizing | 0.999 | D | 0.768 | deleterious | None | None | None | None | N |
| I/Y | 0.8756 | likely_pathogenic | 0.8595 | pathogenic | -1.094 | Destabilizing | 0.987 | D | 0.767 | 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.