Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28920 | 86983;86984;86985 | chr2:178559374;178559373;178559372 | chr2:179424101;179424100;179424099 |
| N2AB | 27279 | 82060;82061;82062 | chr2:178559374;178559373;178559372 | chr2:179424101;179424100;179424099 |
| N2A | 26352 | 79279;79280;79281 | chr2:178559374;178559373;178559372 | chr2:179424101;179424100;179424099 |
| N2B | 19855 | 59788;59789;59790 | chr2:178559374;178559373;178559372 | chr2:179424101;179424100;179424099 |
| Novex-1 | 19980 | 60163;60164;60165 | chr2:178559374;178559373;178559372 | chr2:179424101;179424100;179424099 |
| Novex-2 | 20047 | 60364;60365;60366 | chr2:178559374;178559373;178559372 | chr2:179424101;179424100;179424099 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/C | rs1396089552  |
-0.935 | 0.004 | N | 0.615 | 0.134 | 0.193865811164 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/C | rs1396089552 |
-0.935 | 0.004 | N | 0.615 | 0.134 | 0.193865811164 | gnomAD-4.0.0 | 1.59267E-06 | None | None | None | None | N | None | 0 | 2.28843E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0762 | likely_benign | 0.0835 | benign | -1.434 | Destabilizing | 0.001 | N | 0.253 | neutral | N | 0.455294115 | None | None | N |
| S/C | 0.0726 | likely_benign | 0.0685 | benign | -1.129 | Destabilizing | 0.004 | N | 0.615 | neutral | N | 0.494892653 | None | None | N |
| S/D | 0.8344 | likely_pathogenic | 0.8352 | pathogenic | -2.189 | Highly Destabilizing | 0.418 | N | 0.611 | neutral | None | None | None | None | N |
| S/E | 0.8123 | likely_pathogenic | 0.8189 | pathogenic | -1.934 | Destabilizing | 0.418 | N | 0.619 | neutral | None | None | None | None | N |
| S/F | 0.1922 | likely_benign | 0.2104 | benign | -0.869 | Destabilizing | 0.002 | N | 0.65 | neutral | N | 0.46087608 | None | None | N |
| S/G | 0.1578 | likely_benign | 0.1576 | benign | -1.816 | Destabilizing | 0.129 | N | 0.557 | neutral | None | None | None | None | N |
| S/H | 0.4984 | ambiguous | 0.496 | ambiguous | -1.876 | Destabilizing | 0.94 | D | 0.714 | prob.delet. | None | None | None | None | N |
| S/I | 0.231 | likely_benign | 0.2406 | benign | -0.42 | Destabilizing | 0.264 | N | 0.713 | prob.delet. | None | None | None | None | N |
| S/K | 0.8437 | likely_pathogenic | 0.8336 | pathogenic | -0.793 | Destabilizing | 0.418 | N | 0.613 | neutral | None | None | None | None | N |
| S/L | 0.0987 | likely_benign | 0.0998 | benign | -0.42 | Destabilizing | 0.129 | N | 0.703 | prob.neutral | None | None | None | None | N |
| S/M | 0.1756 | likely_benign | 0.1772 | benign | -0.757 | Destabilizing | 0.061 | N | 0.634 | neutral | None | None | None | None | N |
| S/N | 0.3591 | ambiguous | 0.3396 | benign | -1.594 | Destabilizing | 0.418 | N | 0.617 | neutral | None | None | None | None | N |
| S/P | 0.9776 | likely_pathogenic | 0.9801 | pathogenic | -0.731 | Destabilizing | 0.794 | D | 0.741 | deleterious | N | 0.485611926 | None | None | N |
| S/Q | 0.6435 | likely_pathogenic | 0.6361 | pathogenic | -1.123 | Destabilizing | 0.836 | D | 0.667 | neutral | None | None | None | None | N |
| S/R | 0.7346 | likely_pathogenic | 0.6921 | pathogenic | -1.265 | Destabilizing | 0.716 | D | 0.743 | deleterious | None | None | None | None | N |
| S/T | 0.0936 | likely_benign | 0.0902 | benign | -1.225 | Destabilizing | None | N | 0.196 | neutral | N | 0.42043218 | None | None | N |
| S/V | 0.209 | likely_benign | 0.2252 | benign | -0.731 | Destabilizing | 0.129 | N | 0.701 | prob.neutral | None | None | None | None | N |
| S/W | 0.3724 | ambiguous | 0.3756 | ambiguous | -1.286 | Destabilizing | 0.983 | D | 0.746 | deleterious | None | None | None | None | N |
| S/Y | 0.2288 | likely_benign | 0.2474 | benign | -0.897 | Destabilizing | 0.487 | N | 0.739 | prob.delet. | N | 0.496642092 | 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.