Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30643 | 92152;92153;92154 | chr2:178549795;178549794;178549793 | chr2:179414522;179414521;179414520 |
| N2AB | 29002 | 87229;87230;87231 | chr2:178549795;178549794;178549793 | chr2:179414522;179414521;179414520 |
| N2A | 28075 | 84448;84449;84450 | chr2:178549795;178549794;178549793 | chr2:179414522;179414521;179414520 |
| N2B | 21578 | 64957;64958;64959 | chr2:178549795;178549794;178549793 | chr2:179414522;179414521;179414520 |
| Novex-1 | 21703 | 65332;65333;65334 | chr2:178549795;178549794;178549793 | chr2:179414522;179414521;179414520 |
| Novex-2 | 21770 | 65533;65534;65535 | chr2:178549795;178549794;178549793 | chr2:179414522;179414521;179414520 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/D | None | None | 0.984 | N | 0.623 | 0.305 | 0.653762920561 | gnomAD-4.0.0 | 1.37123E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.01427E-07 | 1.16131E-05 | 0 |
| A/V | rs750203753  |
-0.112 | 0.946 | N | 0.473 | 0.273 | 0.496891249646 | gnomAD-2.1.1 | 3.22E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 6.56E-05 | None | 4.66E-05 | 4.45E-05 | 0 |
| A/V | rs750203753 |
-0.112 | 0.946 | N | 0.473 | 0.273 | 0.496891249646 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 2.07555E-04 | 0 |
| A/V | rs750203753 |
-0.112 | 0.946 | N | 0.473 | 0.273 | 0.496891249646 | gnomAD-4.0.0 | 2.1728E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.29323E-05 | 6.59892E-05 | 3.20914E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.404 | ambiguous | 0.3696 | ambiguous | -0.907 | Destabilizing | 0.999 | D | 0.549 | neutral | None | None | None | None | I |
| A/D | 0.2064 | likely_benign | 0.2521 | benign | -1.517 | Destabilizing | 0.984 | D | 0.623 | neutral | N | 0.473018307 | None | None | I |
| A/E | 0.1562 | likely_benign | 0.1788 | benign | -1.467 | Destabilizing | 0.919 | D | 0.556 | neutral | None | None | None | None | I |
| A/F | 0.2718 | likely_benign | 0.2836 | benign | -0.907 | Destabilizing | 0.996 | D | 0.706 | prob.neutral | None | None | None | None | I |
| A/G | 0.1403 | likely_benign | 0.1381 | benign | -1.293 | Destabilizing | 0.896 | D | 0.493 | neutral | N | 0.498511748 | None | None | I |
| A/H | 0.3351 | likely_benign | 0.3233 | benign | -1.459 | Destabilizing | 0.999 | D | 0.698 | prob.neutral | None | None | None | None | I |
| A/I | 0.1548 | likely_benign | 0.1594 | benign | -0.185 | Destabilizing | 0.988 | D | 0.641 | neutral | None | None | None | None | I |
| A/K | 0.2349 | likely_benign | 0.2445 | benign | -1.338 | Destabilizing | 0.919 | D | 0.553 | neutral | None | None | None | None | I |
| A/L | 0.1288 | likely_benign | 0.1273 | benign | -0.185 | Destabilizing | 0.919 | D | 0.553 | neutral | None | None | None | None | I |
| A/M | 0.1591 | likely_benign | 0.1584 | benign | -0.228 | Destabilizing | 0.999 | D | 0.655 | neutral | None | None | None | None | I |
| A/N | 0.1924 | likely_benign | 0.1984 | benign | -1.205 | Destabilizing | 0.988 | D | 0.699 | prob.neutral | None | None | None | None | I |
| A/P | 0.1069 | likely_benign | 0.1014 | benign | -0.402 | Destabilizing | 0.004 | N | 0.291 | neutral | N | 0.353993757 | None | None | I |
| A/Q | 0.2155 | likely_benign | 0.2062 | benign | -1.246 | Destabilizing | 0.988 | D | 0.661 | neutral | None | None | None | None | I |
| A/R | 0.2658 | likely_benign | 0.2734 | benign | -1.076 | Destabilizing | 0.988 | D | 0.655 | neutral | None | None | None | None | I |
| A/S | 0.0975 | likely_benign | 0.0946 | benign | -1.554 | Destabilizing | 0.896 | D | 0.503 | neutral | N | 0.492873855 | None | None | I |
| A/T | 0.0809 | likely_benign | 0.0832 | benign | -1.391 | Destabilizing | 0.896 | D | 0.476 | neutral | N | 0.504899003 | None | None | I |
| A/V | 0.0945 | likely_benign | 0.0976 | benign | -0.402 | Destabilizing | 0.946 | D | 0.473 | neutral | N | 0.511806333 | None | None | I |
| A/W | 0.6819 | likely_pathogenic | 0.6714 | pathogenic | -1.37 | Destabilizing | 0.999 | D | 0.734 | prob.delet. | None | None | None | None | I |
| A/Y | 0.3441 | ambiguous | 0.3517 | ambiguous | -0.901 | Destabilizing | 0.996 | D | 0.706 | prob.neutral | None | None | None | None | I |
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.