Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29300 | 88123;88124;88125 | chr2:178557364;178557363;178557362 | chr2:179422091;179422090;179422089 |
| N2AB | 27659 | 83200;83201;83202 | chr2:178557364;178557363;178557362 | chr2:179422091;179422090;179422089 |
| N2A | 26732 | 80419;80420;80421 | chr2:178557364;178557363;178557362 | chr2:179422091;179422090;179422089 |
| N2B | 20235 | 60928;60929;60930 | chr2:178557364;178557363;178557362 | chr2:179422091;179422090;179422089 |
| Novex-1 | 20360 | 61303;61304;61305 | chr2:178557364;178557363;178557362 | chr2:179422091;179422090;179422089 |
| Novex-2 | 20427 | 61504;61505;61506 | chr2:178557364;178557363;178557362 | chr2:179422091;179422090;179422089 |
| 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/K | rs1428308872  |
-0.373 | 0.477 | N | 0.637 | 0.269 | 0.307016933798 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| T/K | rs1428308872 |
-0.373 | 0.477 | N | 0.637 | 0.269 | 0.307016933798 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| T/K | rs1428308872 |
-0.373 | 0.477 | N | 0.637 | 0.269 | 0.307016933798 | gnomAD-4.0.0 | 1.0247E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.6748E-05 | 0 | 2.84349E-05 |
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 | 0.085 | likely_benign | 0.0862 | benign | -0.458 | Destabilizing | 0.273 | N | 0.477 | neutral | N | 0.514481278 | None | None | N |
| T/C | 0.3618 | ambiguous | 0.4034 | ambiguous | -0.352 | Destabilizing | 0.985 | D | 0.714 | prob.delet. | None | None | None | None | N |
| T/D | 0.4324 | ambiguous | 0.4057 | ambiguous | 0.47 | Stabilizing | 0.547 | D | 0.62 | neutral | None | None | None | None | N |
| T/E | 0.4535 | ambiguous | 0.4269 | ambiguous | 0.41 | Stabilizing | 0.547 | D | 0.622 | neutral | None | None | None | None | N |
| T/F | 0.3624 | ambiguous | 0.365 | ambiguous | -0.862 | Destabilizing | 0.945 | D | 0.772 | deleterious | None | None | None | None | N |
| T/G | 0.1391 | likely_benign | 0.1407 | benign | -0.606 | Destabilizing | 0.547 | D | 0.584 | neutral | None | None | None | None | N |
| T/H | 0.2994 | likely_benign | 0.303 | benign | -0.829 | Destabilizing | 0.985 | D | 0.751 | deleterious | None | None | None | None | N |
| T/I | 0.2876 | likely_benign | 0.296 | benign | -0.185 | Destabilizing | 0.864 | D | 0.747 | deleterious | N | 0.485312892 | None | None | N |
| T/K | 0.321 | likely_benign | 0.3291 | benign | -0.31 | Destabilizing | 0.477 | N | 0.637 | neutral | N | 0.501858698 | None | None | N |
| T/L | 0.1275 | likely_benign | 0.1375 | benign | -0.185 | Destabilizing | 0.707 | D | 0.609 | neutral | None | None | None | None | N |
| T/M | 0.1034 | likely_benign | 0.108 | benign | -0.056 | Destabilizing | 0.995 | D | 0.715 | prob.delet. | None | None | None | None | N |
| T/N | 0.0954 | likely_benign | 0.0911 | benign | -0.147 | Destabilizing | 0.07 | N | 0.312 | neutral | None | None | None | None | N |
| T/P | 0.101 | likely_benign | 0.1005 | benign | -0.247 | Destabilizing | 0.928 | D | 0.747 | deleterious | N | 0.47020715 | None | None | N |
| T/Q | 0.2677 | likely_benign | 0.2624 | benign | -0.347 | Destabilizing | 0.894 | D | 0.749 | deleterious | None | None | None | None | N |
| T/R | 0.335 | likely_benign | 0.3335 | benign | -0.064 | Destabilizing | 0.864 | D | 0.742 | deleterious | D | 0.525100917 | None | None | N |
| T/S | 0.0833 | likely_benign | 0.082 | benign | -0.44 | Destabilizing | 0.006 | N | 0.342 | neutral | N | 0.450352442 | None | None | N |
| T/V | 0.1885 | likely_benign | 0.1977 | benign | -0.247 | Destabilizing | 0.707 | D | 0.517 | neutral | None | None | None | None | N |
| T/W | 0.7223 | likely_pathogenic | 0.7445 | pathogenic | -0.824 | Destabilizing | 0.995 | D | 0.7 | prob.neutral | None | None | None | None | N |
| T/Y | 0.396 | ambiguous | 0.4045 | ambiguous | -0.553 | Destabilizing | 0.945 | D | 0.77 | 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.