Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 5584 | 16975;16976;16977 | chr2:178732219;178732218;178732217 | chr2:179596946;179596945;179596944 |
| N2AB | 5267 | 16024;16025;16026 | chr2:178732219;178732218;178732217 | chr2:179596946;179596945;179596944 |
| N2A | 4340 | 13243;13244;13245 | chr2:178732219;178732218;178732217 | chr2:179596946;179596945;179596944 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/N | rs779652311  |
-2.255 | 0.859 | D | 0.743 | 0.597 | None | gnomAD-2.1.1 | 1.20671E-04 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 9.80392E-04 | None | 0 | 0 | 0 |
| I/N | rs779652311 |
-2.255 | 0.859 | D | 0.743 | 0.597 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07555E-04 | 0 |
| I/N | rs779652311 |
-2.255 | 0.859 | D | 0.743 | 0.597 | None | gnomAD-4.0.0 | 5.14352E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 9.11347E-04 | 0 |
| I/V | rs368116422 |
-1.592 | 0.004 | D | 0.238 | 0.141 | None | 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/V | rs368116422 |
-1.592 | 0.004 | D | 0.238 | 0.141 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs368116422 |
-1.592 | 0.004 | D | 0.238 | 0.141 | None | gnomAD-4.0.0 | 1.54916E-05 | None | None | None | None | N | None | 0 | 1.66678E-05 | None | 0 | 0 | None | 0 | 0 | 2.03422E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.7589 | likely_pathogenic | 0.8233 | pathogenic | -2.502 | Highly Destabilizing | 0.272 | N | 0.537 | neutral | None | None | None | None | N |
| I/C | 0.8307 | likely_pathogenic | 0.8802 | pathogenic | -1.436 | Destabilizing | 0.968 | D | 0.629 | neutral | None | None | None | None | N |
| I/D | 0.9659 | likely_pathogenic | 0.975 | pathogenic | -2.963 | Highly Destabilizing | 0.89 | D | 0.74 | deleterious | None | None | None | None | N |
| I/E | 0.8974 | likely_pathogenic | 0.9212 | pathogenic | -2.761 | Highly Destabilizing | 0.726 | D | 0.717 | prob.delet. | None | None | None | None | N |
| I/F | 0.2968 | likely_benign | 0.3188 | benign | -1.631 | Destabilizing | 0.331 | N | 0.559 | neutral | N | 0.517109262 | None | None | N |
| I/G | 0.9117 | likely_pathogenic | 0.9413 | pathogenic | -2.99 | Highly Destabilizing | 0.726 | D | 0.709 | prob.delet. | None | None | None | None | N |
| I/H | 0.8772 | likely_pathogenic | 0.9119 | pathogenic | -2.425 | Highly Destabilizing | 0.968 | D | 0.724 | prob.delet. | None | None | None | None | N |
| I/K | 0.7867 | likely_pathogenic | 0.8224 | pathogenic | -1.869 | Destabilizing | 0.726 | D | 0.712 | prob.delet. | None | None | None | None | N |
| I/L | 0.0842 | likely_benign | 0.1114 | benign | -1.087 | Destabilizing | None | N | 0.213 | neutral | N | 0.451091522 | None | None | N |
| I/M | 0.1048 | likely_benign | 0.1219 | benign | -0.785 | Destabilizing | 0.331 | N | 0.584 | neutral | N | 0.503359873 | None | None | N |
| I/N | 0.7606 | likely_pathogenic | 0.791 | pathogenic | -2.123 | Highly Destabilizing | 0.859 | D | 0.743 | deleterious | D | 0.539519158 | None | None | N |
| I/P | 0.9559 | likely_pathogenic | 0.967 | pathogenic | -1.543 | Destabilizing | 0.89 | D | 0.743 | deleterious | None | None | None | None | N |
| I/Q | 0.8009 | likely_pathogenic | 0.847 | pathogenic | -2.063 | Highly Destabilizing | 0.89 | D | 0.742 | deleterious | None | None | None | None | N |
| I/R | 0.7158 | likely_pathogenic | 0.77 | pathogenic | -1.531 | Destabilizing | 0.726 | D | 0.743 | deleterious | None | None | None | None | N |
| I/S | 0.8317 | likely_pathogenic | 0.8691 | pathogenic | -2.718 | Highly Destabilizing | 0.667 | D | 0.643 | neutral | N | 0.516134984 | None | None | N |
| I/T | 0.7601 | likely_pathogenic | 0.8105 | pathogenic | -2.387 | Highly Destabilizing | 0.22 | N | 0.579 | neutral | D | 0.536223794 | None | None | N |
| I/V | 0.1232 | likely_benign | 0.1398 | benign | -1.543 | Destabilizing | 0.004 | N | 0.238 | neutral | D | 0.532982186 | None | None | N |
| I/W | 0.8237 | likely_pathogenic | 0.8755 | pathogenic | -2.038 | Highly Destabilizing | 0.968 | D | 0.714 | prob.delet. | None | None | None | None | N |
| I/Y | 0.6921 | likely_pathogenic | 0.7379 | pathogenic | -1.729 | Destabilizing | 0.726 | D | 0.673 | neutral | 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.