Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18447 | 55564;55565;55566 | chr2:178601751;178601750;178601749 | chr2:179466478;179466477;179466476 |
| N2AB | 16806 | 50641;50642;50643 | chr2:178601751;178601750;178601749 | chr2:179466478;179466477;179466476 |
| N2A | 15879 | 47860;47861;47862 | chr2:178601751;178601750;178601749 | chr2:179466478;179466477;179466476 |
| N2B | 9382 | 28369;28370;28371 | chr2:178601751;178601750;178601749 | chr2:179466478;179466477;179466476 |
| Novex-1 | 9507 | 28744;28745;28746 | chr2:178601751;178601750;178601749 | chr2:179466478;179466477;179466476 |
| Novex-2 | 9574 | 28945;28946;28947 | chr2:178601751;178601750;178601749 | chr2:179466478;179466477;179466476 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | rs2053509362  |
None | 0.006 | N | 0.363 | 0.255 | 0.260735089382 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/A | rs2053509362 |
None | 0.006 | N | 0.363 | 0.255 | 0.260735089382 | gnomAD-4.0.0 | 1.86542E-06 | None | None | None | None | N | None | 2.68536E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.11757E-05 | 0 |
| P/L | rs397517622 |
-0.787 | 0.947 | D | 0.724 | 0.394 | 0.634485840324 | gnomAD-2.1.1 | 2.46E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.36528E-04 | None | 0 | 1.81E-05 | 0 |
| P/L | rs397517622 |
-0.787 | 0.947 | D | 0.724 | 0.394 | 0.634485840324 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| P/L | rs397517622 |
-0.787 | 0.947 | D | 0.724 | 0.394 | 0.634485840324 | gnomAD-4.0.0 | 3.29571E-05 | None | None | None | None | N | None | 1.34261E-05 | 0 | None | 0 | 2.23874E-05 | None | 0 | 1.65399E-04 | 3.22559E-05 | 1.34111E-04 | 0 |
| P/R | rs397517622 |
-0.604 | 0.942 | N | 0.743 | 0.436 | 0.476051820916 | gnomAD-2.1.1 | 8.22E-06 | None | None | None | None | N | None | 0 | 5.95E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/R | rs397517622 |
-0.604 | 0.942 | N | 0.743 | 0.436 | 0.476051820916 | gnomAD-4.0.0 | 2.06011E-06 | None | None | None | None | N | None | 0 | 4.55311E-05 | None | 0 | 0 | None | 0 | 0 | 9.00792E-07 | 0 | 0 |
| P/S | None | None | 0.477 | N | 0.591 | 0.32 | 0.306053231325 | gnomAD-4.0.0 | 6.8668E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00763E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.118 | likely_benign | 0.1218 | benign | -1.387 | Destabilizing | 0.006 | N | 0.363 | neutral | N | 0.504062002 | None | None | N |
| P/C | 0.6781 | likely_pathogenic | 0.5945 | pathogenic | -0.87 | Destabilizing | 0.985 | D | 0.754 | deleterious | None | None | None | None | N |
| P/D | 0.4243 | ambiguous | 0.3846 | ambiguous | -1.399 | Destabilizing | 0.809 | D | 0.704 | prob.neutral | None | None | None | None | N |
| P/E | 0.2995 | likely_benign | 0.2731 | benign | -1.45 | Destabilizing | 0.894 | D | 0.706 | prob.neutral | None | None | None | None | N |
| P/F | 0.6935 | likely_pathogenic | 0.658 | pathogenic | -1.212 | Destabilizing | 0.985 | D | 0.75 | deleterious | None | None | None | None | N |
| P/G | 0.2857 | likely_benign | 0.2665 | benign | -1.652 | Destabilizing | 0.547 | D | 0.568 | neutral | None | None | None | None | N |
| P/H | 0.2534 | likely_benign | 0.2142 | benign | -1.185 | Destabilizing | 0.97 | D | 0.731 | prob.delet. | None | None | None | None | N |
| P/I | 0.5554 | ambiguous | 0.5376 | ambiguous | -0.779 | Destabilizing | 0.894 | D | 0.783 | deleterious | None | None | None | None | N |
| P/K | 0.2776 | likely_benign | 0.2432 | benign | -1.211 | Destabilizing | 0.809 | D | 0.704 | prob.neutral | None | None | None | None | N |
| P/L | 0.2 | likely_benign | 0.1955 | benign | -0.779 | Destabilizing | 0.947 | D | 0.724 | prob.delet. | D | 0.53421155 | None | None | N |
| P/M | 0.4452 | ambiguous | 0.4154 | ambiguous | -0.519 | Destabilizing | 0.985 | D | 0.722 | prob.delet. | None | None | None | None | N |
| P/N | 0.3062 | likely_benign | 0.2535 | benign | -0.898 | Destabilizing | 0.017 | N | 0.405 | neutral | None | None | None | None | N |
| P/Q | 0.19 | likely_benign | 0.1666 | benign | -1.158 | Destabilizing | 0.942 | D | 0.768 | deleterious | N | 0.500919748 | None | None | N |
| P/R | 0.2087 | likely_benign | 0.1811 | benign | -0.581 | Destabilizing | 0.942 | D | 0.743 | deleterious | N | 0.508737103 | None | None | N |
| P/S | 0.1421 | likely_benign | 0.1294 | benign | -1.329 | Destabilizing | 0.477 | N | 0.591 | neutral | N | 0.517393871 | None | None | N |
| P/T | 0.1382 | likely_benign | 0.133 | benign | -1.285 | Destabilizing | 0.645 | D | 0.656 | neutral | N | 0.512046767 | None | None | N |
| P/V | 0.3555 | ambiguous | 0.3502 | ambiguous | -0.947 | Destabilizing | 0.809 | D | 0.681 | prob.neutral | None | None | None | None | N |
| P/W | 0.7383 | likely_pathogenic | 0.7136 | pathogenic | -1.342 | Destabilizing | 0.995 | D | 0.715 | prob.delet. | None | None | None | None | N |
| P/Y | 0.5885 | likely_pathogenic | 0.549 | ambiguous | -1.09 | Destabilizing | 0.995 | D | 0.757 | 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.