Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23321 | 70186;70187;70188 | chr2:178576171;178576170;178576169 | chr2:179440898;179440897;179440896 |
| N2AB | 21680 | 65263;65264;65265 | chr2:178576171;178576170;178576169 | chr2:179440898;179440897;179440896 |
| N2A | 20753 | 62482;62483;62484 | chr2:178576171;178576170;178576169 | chr2:179440898;179440897;179440896 |
| N2B | 14256 | 42991;42992;42993 | chr2:178576171;178576170;178576169 | chr2:179440898;179440897;179440896 |
| Novex-1 | 14381 | 43366;43367;43368 | chr2:178576171;178576170;178576169 | chr2:179440898;179440897;179440896 |
| Novex-2 | 14448 | 43567;43568;43569 | chr2:178576171;178576170;178576169 | chr2:179440898;179440897;179440896 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/H | None | None | 0.946 | N | 0.424 | 0.327 | 0.312001716656 | gnomAD-4.0.0 | 3.42293E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.49894E-06 | 0 | 0 |
| D/N | rs571879486  |
0.24 | 0.844 | N | 0.322 | 0.199 | 0.239901079897 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 2.91E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/N | rs571879486 |
0.24 | 0.844 | N | 0.322 | 0.199 | 0.239901079897 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/N | rs571879486 |
0.24 | 0.844 | N | 0.322 | 0.199 | 0.239901079897 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| D/N | rs571879486 |
0.24 | 0.844 | N | 0.322 | 0.199 | 0.239901079897 | gnomAD-4.0.0 | 3.71995E-06 | None | None | None | None | I | None | 0 | 1.66856E-05 | None | 0 | 0 | None | 0 | 0 | 2.54375E-06 | 2.19916E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.051 | likely_benign | 0.0506 | benign | -0.122 | Destabilizing | None | N | 0.201 | neutral | N | 0.350841596 | None | None | I |
| D/C | 0.3552 | ambiguous | 0.3328 | benign | 0.173 | Stabilizing | 0.972 | D | 0.489 | neutral | None | None | None | None | I |
| D/E | 0.0931 | likely_benign | 0.0929 | benign | -0.23 | Destabilizing | 0.001 | N | 0.087 | neutral | N | 0.370043432 | None | None | I |
| D/F | 0.3601 | ambiguous | 0.3525 | ambiguous | -0.222 | Destabilizing | 0.901 | D | 0.521 | neutral | None | None | None | None | I |
| D/G | 0.0918 | likely_benign | 0.0889 | benign | -0.275 | Destabilizing | 0.166 | N | 0.445 | neutral | N | 0.447133205 | None | None | I |
| D/H | 0.1345 | likely_benign | 0.1274 | benign | 0.048 | Stabilizing | 0.946 | D | 0.424 | neutral | N | 0.487523964 | None | None | I |
| D/I | 0.1648 | likely_benign | 0.1575 | benign | 0.218 | Stabilizing | 0.818 | D | 0.524 | neutral | None | None | None | None | I |
| D/K | 0.1419 | likely_benign | 0.1333 | benign | 0.502 | Stabilizing | 0.209 | N | 0.446 | neutral | None | None | None | None | I |
| D/L | 0.1755 | likely_benign | 0.1674 | benign | 0.218 | Stabilizing | 0.561 | D | 0.575 | neutral | None | None | None | None | I |
| D/M | 0.2971 | likely_benign | 0.2982 | benign | 0.3 | Stabilizing | 0.965 | D | 0.495 | neutral | None | None | None | None | I |
| D/N | 0.0794 | likely_benign | 0.077 | benign | 0.303 | Stabilizing | 0.844 | D | 0.322 | neutral | N | 0.47291987 | None | None | I |
| D/P | 0.4726 | ambiguous | 0.4901 | ambiguous | 0.126 | Stabilizing | 0.722 | D | 0.476 | neutral | None | None | None | None | I |
| D/Q | 0.1452 | likely_benign | 0.144 | benign | 0.305 | Stabilizing | 0.39 | N | 0.325 | neutral | None | None | None | None | I |
| D/R | 0.1683 | likely_benign | 0.1618 | benign | 0.616 | Stabilizing | 0.561 | D | 0.513 | neutral | None | None | None | None | I |
| D/S | 0.0628 | likely_benign | 0.0615 | benign | 0.199 | Stabilizing | 0.021 | N | 0.083 | neutral | None | None | None | None | I |
| D/T | 0.106 | likely_benign | 0.1034 | benign | 0.316 | Stabilizing | 0.209 | N | 0.447 | neutral | None | None | None | None | I |
| D/V | 0.096 | likely_benign | 0.0913 | benign | 0.126 | Stabilizing | 0.326 | N | 0.574 | neutral | N | 0.436095066 | None | None | I |
| D/W | 0.7492 | likely_pathogenic | 0.7365 | pathogenic | -0.154 | Destabilizing | 0.991 | D | 0.548 | neutral | None | None | None | None | I |
| D/Y | 0.1449 | likely_benign | 0.1367 | benign | 0.01 | Stabilizing | 0.982 | D | 0.516 | neutral | N | 0.499087751 | None | None | I |
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.