Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2675 | 8248;8249;8250 | chr2:178771304;178771303;178771302 | chr2:179636031;179636030;179636029 |
| N2AB | 2675 | 8248;8249;8250 | chr2:178771304;178771303;178771302 | chr2:179636031;179636030;179636029 |
| N2A | 2675 | 8248;8249;8250 | chr2:178771304;178771303;178771302 | chr2:179636031;179636030;179636029 |
| N2B | 2629 | 8110;8111;8112 | chr2:178771304;178771303;178771302 | chr2:179636031;179636030;179636029 |
| Novex-1 | 2629 | 8110;8111;8112 | chr2:178771304;178771303;178771302 | chr2:179636031;179636030;179636029 |
| Novex-2 | 2629 | 8110;8111;8112 | chr2:178771304;178771303;178771302 | chr2:179636031;179636030;179636029 |
| Novex-3 | 2675 | 8248;8249;8250 | chr2:178771304;178771303;178771302 | chr2:179636031;179636030;179636029 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | rs375223745  |
None | 0.722 | D | 0.673 | 0.538 | None | 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 |
| R/G | rs375223745 |
None | 0.722 | D | 0.673 | 0.538 | None | gnomAD-4.0.0 | 2.56122E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.78343E-06 | 0 | 0 |
| R/S | rs2154343309 |
None | 0.565 | N | 0.62 | 0.34 | 0.276482976112 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.4794 | ambiguous | 0.4687 | ambiguous | -1.479 | Destabilizing | 0.633 | D | 0.651 | neutral | None | None | None | None | N |
| R/C | 0.1495 | likely_benign | 0.1408 | benign | -1.718 | Destabilizing | 0.996 | D | 0.767 | deleterious | None | None | None | None | N |
| R/D | 0.8048 | likely_pathogenic | 0.7739 | pathogenic | -0.865 | Destabilizing | 0.923 | D | 0.703 | prob.neutral | None | None | None | None | N |
| R/E | 0.3961 | ambiguous | 0.3657 | ambiguous | -0.708 | Destabilizing | 0.633 | D | 0.647 | neutral | None | None | None | None | N |
| R/F | 0.503 | ambiguous | 0.4829 | ambiguous | -1.148 | Destabilizing | 0.987 | D | 0.779 | deleterious | None | None | None | None | N |
| R/G | 0.4275 | ambiguous | 0.3853 | ambiguous | -1.798 | Destabilizing | 0.722 | D | 0.673 | neutral | D | 0.587981448 | None | None | N |
| R/H | 0.1058 | likely_benign | 0.0983 | benign | -1.744 | Destabilizing | 0.961 | D | 0.63 | neutral | None | None | None | None | N |
| R/I | 0.1902 | likely_benign | 0.188 | benign | -0.592 | Destabilizing | 0.949 | D | 0.773 | deleterious | N | 0.514021934 | None | None | N |
| R/K | 0.09 | likely_benign | 0.0948 | benign | -1.551 | Destabilizing | 0.008 | N | 0.301 | neutral | N | 0.491205901 | None | None | N |
| R/L | 0.2453 | likely_benign | 0.2264 | benign | -0.592 | Destabilizing | 0.775 | D | 0.673 | neutral | None | None | None | None | N |
| R/M | 0.2551 | likely_benign | 0.2475 | benign | -0.953 | Destabilizing | 0.996 | D | 0.709 | prob.delet. | None | None | None | None | N |
| R/N | 0.5557 | ambiguous | 0.5531 | ambiguous | -1.216 | Destabilizing | 0.775 | D | 0.592 | neutral | None | None | None | None | N |
| R/P | 0.9799 | likely_pathogenic | 0.9678 | pathogenic | -0.871 | Destabilizing | 0.961 | D | 0.757 | deleterious | None | None | None | None | N |
| R/Q | 0.0965 | likely_benign | 0.0922 | benign | -1.277 | Destabilizing | 0.096 | N | 0.399 | neutral | None | None | None | None | N |
| R/S | 0.4734 | ambiguous | 0.4547 | ambiguous | -2.023 | Highly Destabilizing | 0.565 | D | 0.62 | neutral | N | 0.481099561 | None | None | N |
| R/T | 0.2065 | likely_benign | 0.2029 | benign | -1.675 | Destabilizing | 0.722 | D | 0.643 | neutral | N | 0.492651297 | None | None | N |
| R/V | 0.2875 | likely_benign | 0.2763 | benign | -0.871 | Destabilizing | 0.923 | D | 0.725 | prob.delet. | None | None | None | None | N |
| R/W | 0.2029 | likely_benign | 0.1761 | benign | -0.736 | Destabilizing | 0.996 | D | 0.741 | deleterious | None | None | None | None | N |
| R/Y | 0.361 | ambiguous | 0.334 | benign | -0.459 | Destabilizing | 0.987 | D | 0.759 | 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.