Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22070 | 66433;66434;66435 | chr2:178582161;178582160;178582159 | chr2:179446888;179446887;179446886 |
| N2AB | 20429 | 61510;61511;61512 | chr2:178582161;178582160;178582159 | chr2:179446888;179446887;179446886 |
| N2A | 19502 | 58729;58730;58731 | chr2:178582161;178582160;178582159 | chr2:179446888;179446887;179446886 |
| N2B | 13005 | 39238;39239;39240 | chr2:178582161;178582160;178582159 | chr2:179446888;179446887;179446886 |
| Novex-1 | 13130 | 39613;39614;39615 | chr2:178582161;178582160;178582159 | chr2:179446888;179446887;179446886 |
| Novex-2 | 13197 | 39814;39815;39816 | chr2:178582161;178582160;178582159 | chr2:179446888;179446887;179446886 |
| 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 | rs750035436  |
-0.739 | 0.986 | N | 0.479 | 0.315 | 0.331619326243 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.97E-06 | 0 |
| D/H | rs750035436 |
-0.739 | 0.986 | N | 0.479 | 0.315 | 0.331619326243 | gnomAD-4.0.0 | 6.84644E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99674E-07 | 0 | 0 |
| D/N | rs750035436 |
-0.211 | 0.075 | N | 0.217 | 0.15 | 0.208000267992 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.97E-06 | 0 |
| D/N | rs750035436 |
-0.211 | 0.075 | N | 0.217 | 0.15 | 0.208000267992 | gnomAD-4.0.0 | 2.05393E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69902E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.4885 | ambiguous | 0.5001 | ambiguous | -0.332 | Destabilizing | 0.565 | D | 0.448 | neutral | N | 0.470509865 | None | None | N |
| D/C | 0.8613 | likely_pathogenic | 0.8746 | pathogenic | -0.076 | Destabilizing | 0.996 | D | 0.665 | neutral | None | None | None | None | N |
| D/E | 0.2135 | likely_benign | 0.2304 | benign | -0.852 | Destabilizing | 0.008 | N | 0.193 | neutral | N | 0.454200824 | None | None | N |
| D/F | 0.8143 | likely_pathogenic | 0.8446 | pathogenic | -0.528 | Destabilizing | 0.923 | D | 0.606 | neutral | None | None | None | None | N |
| D/G | 0.3949 | ambiguous | 0.391 | ambiguous | -0.614 | Destabilizing | 0.722 | D | 0.453 | neutral | N | 0.495586086 | None | None | N |
| D/H | 0.6361 | likely_pathogenic | 0.6417 | pathogenic | -0.926 | Destabilizing | 0.986 | D | 0.479 | neutral | N | 0.502128057 | None | None | N |
| D/I | 0.7543 | likely_pathogenic | 0.7729 | pathogenic | 0.38 | Stabilizing | 0.675 | D | 0.546 | neutral | None | None | None | None | N |
| D/K | 0.7756 | likely_pathogenic | 0.7796 | pathogenic | -0.371 | Destabilizing | 0.633 | D | 0.454 | neutral | None | None | None | None | N |
| D/L | 0.6778 | likely_pathogenic | 0.7161 | pathogenic | 0.38 | Stabilizing | 0.858 | D | 0.482 | neutral | None | None | None | None | N |
| D/M | 0.8271 | likely_pathogenic | 0.8485 | pathogenic | 0.824 | Stabilizing | 0.979 | D | 0.597 | neutral | None | None | None | None | N |
| D/N | 0.1643 | likely_benign | 0.1802 | benign | -0.568 | Destabilizing | 0.075 | N | 0.217 | neutral | N | 0.453736677 | None | None | N |
| D/P | 0.9865 | likely_pathogenic | 0.9895 | pathogenic | 0.168 | Stabilizing | 0.961 | D | 0.491 | neutral | None | None | None | None | N |
| D/Q | 0.6344 | likely_pathogenic | 0.6371 | pathogenic | -0.5 | Destabilizing | 0.858 | D | 0.477 | neutral | None | None | None | None | N |
| D/R | 0.8193 | likely_pathogenic | 0.8215 | pathogenic | -0.374 | Destabilizing | 0.923 | D | 0.563 | neutral | None | None | None | None | N |
| D/S | 0.2725 | likely_benign | 0.2856 | benign | -0.773 | Destabilizing | 0.775 | D | 0.451 | neutral | None | None | None | None | N |
| D/T | 0.3888 | ambiguous | 0.4071 | ambiguous | -0.56 | Destabilizing | 0.775 | D | 0.46 | neutral | None | None | None | None | N |
| D/V | 0.5855 | likely_pathogenic | 0.595 | pathogenic | 0.168 | Stabilizing | 0.018 | N | 0.363 | neutral | N | 0.510098963 | None | None | N |
| D/W | 0.9554 | likely_pathogenic | 0.9619 | pathogenic | -0.565 | Destabilizing | 0.996 | D | 0.681 | prob.neutral | None | None | None | None | N |
| D/Y | 0.4405 | ambiguous | 0.4621 | ambiguous | -0.35 | Destabilizing | 0.949 | D | 0.608 | neutral | N | 0.487132863 | 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.