Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2451 | 7576;7577;7578 | chr2:178773705;178773704;178773703 | chr2:179638432;179638431;179638430 |
| N2AB | 2451 | 7576;7577;7578 | chr2:178773705;178773704;178773703 | chr2:179638432;179638431;179638430 |
| N2A | 2451 | 7576;7577;7578 | chr2:178773705;178773704;178773703 | chr2:179638432;179638431;179638430 |
| N2B | 2405 | 7438;7439;7440 | chr2:178773705;178773704;178773703 | chr2:179638432;179638431;179638430 |
| Novex-1 | 2405 | 7438;7439;7440 | chr2:178773705;178773704;178773703 | chr2:179638432;179638431;179638430 |
| Novex-2 | 2405 | 7438;7439;7440 | chr2:178773705;178773704;178773703 | chr2:179638432;179638431;179638430 |
| Novex-3 | 2451 | 7576;7577;7578 | chr2:178773705;178773704;178773703 | chr2:179638432;179638431;179638430 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/P | rs2091856215  |
None | 1.0 | N | 0.91 | 0.609 | 0.653458178305 | 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 |
| L/P | rs2091856215 |
None | 1.0 | N | 0.91 | 0.609 | 0.653458178305 | gnomAD-4.0.0 | 6.57091E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47003E-05 | 0 | 0 |
| L/V | rs1334983406 |
-1.716 | 0.999 | D | 0.473 | 0.306 | 0.441844919209 | gnomAD-2.1.1 | 1.2E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.6372E-04 | None | 0 | None | 0 | 0 | 0 |
| L/V | rs1334983406 |
-1.716 | 0.999 | D | 0.473 | 0.306 | 0.441844919209 | gnomAD-4.0.0 | 4.77219E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 8.32732E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.8631 | likely_pathogenic | 0.8428 | pathogenic | -2.258 | Highly Destabilizing | 0.999 | D | 0.684 | prob.neutral | None | None | None | None | N |
| L/C | 0.899 | likely_pathogenic | 0.8851 | pathogenic | -1.555 | Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | N |
| L/D | 0.9981 | likely_pathogenic | 0.998 | pathogenic | -2.326 | Highly Destabilizing | 1.0 | D | 0.907 | deleterious | None | None | None | None | N |
| L/E | 0.985 | likely_pathogenic | 0.9837 | pathogenic | -2.243 | Highly Destabilizing | 1.0 | D | 0.906 | deleterious | None | None | None | None | N |
| L/F | 0.6604 | likely_pathogenic | 0.6327 | pathogenic | -1.553 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | N |
| L/G | 0.9765 | likely_pathogenic | 0.9738 | pathogenic | -2.682 | Highly Destabilizing | 1.0 | D | 0.895 | deleterious | None | None | None | None | N |
| L/H | 0.978 | likely_pathogenic | 0.9755 | pathogenic | -2.038 | Highly Destabilizing | 1.0 | D | 0.879 | deleterious | None | None | None | None | N |
| L/I | 0.2405 | likely_benign | 0.2166 | benign | -1.103 | Destabilizing | 0.999 | D | 0.493 | neutral | D | 0.554087847 | None | None | N |
| L/K | 0.9802 | likely_pathogenic | 0.9799 | pathogenic | -1.715 | Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | None | N |
| L/M | 0.3002 | likely_benign | 0.2851 | benign | -0.891 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| L/N | 0.9857 | likely_pathogenic | 0.9851 | pathogenic | -1.71 | Destabilizing | 1.0 | D | 0.909 | deleterious | None | None | None | None | N |
| L/P | 0.8309 | likely_pathogenic | 0.8169 | pathogenic | -1.462 | Destabilizing | 1.0 | D | 0.91 | deleterious | N | 0.428319106 | None | None | N |
| L/Q | 0.9366 | likely_pathogenic | 0.9322 | pathogenic | -1.806 | Destabilizing | 1.0 | D | 0.897 | deleterious | D | 0.635083753 | None | None | N |
| L/R | 0.9669 | likely_pathogenic | 0.9646 | pathogenic | -1.173 | Destabilizing | 1.0 | D | 0.893 | deleterious | D | 0.673671726 | None | None | N |
| L/S | 0.9657 | likely_pathogenic | 0.9594 | pathogenic | -2.341 | Highly Destabilizing | 1.0 | D | 0.866 | deleterious | None | None | None | None | N |
| L/T | 0.9145 | likely_pathogenic | 0.9009 | pathogenic | -2.134 | Highly Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| L/V | 0.2932 | likely_benign | 0.261 | benign | -1.462 | Destabilizing | 0.999 | D | 0.473 | neutral | D | 0.529570156 | None | None | N |
| L/W | 0.9582 | likely_pathogenic | 0.9514 | pathogenic | -1.793 | Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | N |
| L/Y | 0.9789 | likely_pathogenic | 0.976 | pathogenic | -1.546 | Destabilizing | 1.0 | D | 0.861 | 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.