Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20129 | 60610;60611;60612 | chr2:178591340;178591339;178591338 | chr2:179456067;179456066;179456065 |
| N2AB | 18488 | 55687;55688;55689 | chr2:178591340;178591339;178591338 | chr2:179456067;179456066;179456065 |
| N2A | 17561 | 52906;52907;52908 | chr2:178591340;178591339;178591338 | chr2:179456067;179456066;179456065 |
| N2B | 11064 | 33415;33416;33417 | chr2:178591340;178591339;178591338 | chr2:179456067;179456066;179456065 |
| Novex-1 | 11189 | 33790;33791;33792 | chr2:178591340;178591339;178591338 | chr2:179456067;179456066;179456065 |
| Novex-2 | 11256 | 33991;33992;33993 | chr2:178591340;178591339;178591338 | chr2:179456067;179456066;179456065 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs746303359  |
-0.322 | 0.825 | N | 0.626 | 0.308 | 0.33085137897 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.67E-05 | 0 |
| T/A | rs746303359 |
-0.322 | 0.825 | N | 0.626 | 0.308 | 0.33085137897 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| T/A | rs746303359 |
-0.322 | 0.825 | N | 0.626 | 0.308 | 0.33085137897 | gnomAD-4.0.0 | 6.40909E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.19727E-05 | 0 | 0 |
| T/K | None | None | 0.988 | D | 0.665 | 0.426 | 0.412849826617 | gnomAD-4.0.0 | 6.84376E-07 | None | None | None | None | N | None | 2.99079E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/R | rs2050149593 |
None | 0.988 | D | 0.701 | 0.38 | 0.484037581386 | gnomAD-4.0.0 | 2.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.87891E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1041 | likely_benign | 0.1139 | benign | -0.42 | Destabilizing | 0.825 | D | 0.626 | neutral | N | 0.504870078 | None | None | N |
| T/C | 0.4832 | ambiguous | 0.5273 | ambiguous | -0.094 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | N |
| T/D | 0.4089 | ambiguous | 0.4479 | ambiguous | 0.071 | Stabilizing | 0.991 | D | 0.66 | neutral | None | None | None | None | N |
| T/E | 0.3286 | likely_benign | 0.3833 | ambiguous | -0.016 | Destabilizing | 0.991 | D | 0.661 | neutral | None | None | None | None | N |
| T/F | 0.3507 | ambiguous | 0.4063 | ambiguous | -0.988 | Destabilizing | 0.995 | D | 0.769 | deleterious | None | None | None | None | N |
| T/G | 0.2979 | likely_benign | 0.3245 | benign | -0.533 | Destabilizing | 0.938 | D | 0.705 | prob.neutral | None | None | None | None | N |
| T/H | 0.2827 | likely_benign | 0.3176 | benign | -0.955 | Destabilizing | 1.0 | D | 0.758 | deleterious | None | None | None | None | N |
| T/I | 0.2129 | likely_benign | 0.2507 | benign | -0.239 | Destabilizing | 0.994 | D | 0.709 | prob.delet. | N | 0.483401832 | None | None | N |
| T/K | 0.2021 | likely_benign | 0.241 | benign | -0.289 | Destabilizing | 0.988 | D | 0.665 | neutral | D | 0.533056757 | None | None | N |
| T/L | 0.1534 | likely_benign | 0.175 | benign | -0.239 | Destabilizing | 0.968 | D | 0.691 | prob.neutral | None | None | None | None | N |
| T/M | 0.0934 | likely_benign | 0.0972 | benign | 0.169 | Stabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| T/N | 0.1204 | likely_benign | 0.1259 | benign | -0.013 | Destabilizing | 0.991 | D | 0.688 | prob.neutral | None | None | None | None | N |
| T/P | 0.3511 | ambiguous | 0.4147 | ambiguous | -0.273 | Destabilizing | 0.994 | D | 0.703 | prob.neutral | N | 0.519802245 | None | None | N |
| T/Q | 0.2437 | likely_benign | 0.2722 | benign | -0.314 | Destabilizing | 0.991 | D | 0.699 | prob.neutral | None | None | None | None | N |
| T/R | 0.1891 | likely_benign | 0.2332 | benign | -0.026 | Destabilizing | 0.988 | D | 0.701 | prob.neutral | D | 0.533750191 | None | None | N |
| T/S | 0.1212 | likely_benign | 0.1245 | benign | -0.223 | Destabilizing | 0.234 | N | 0.401 | neutral | N | 0.503947359 | None | None | N |
| T/V | 0.1707 | likely_benign | 0.1933 | benign | -0.273 | Destabilizing | 0.968 | D | 0.707 | prob.neutral | None | None | None | None | N |
| T/W | 0.6745 | likely_pathogenic | 0.7241 | pathogenic | -0.973 | Destabilizing | 1.0 | D | 0.738 | prob.delet. | None | None | None | None | N |
| T/Y | 0.3354 | likely_benign | 0.3858 | ambiguous | -0.688 | Destabilizing | 0.998 | D | 0.763 | 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.