Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23780 | 71563;71564;71565 | chr2:178574794;178574793;178574792 | chr2:179439521;179439520;179439519 |
| N2AB | 22139 | 66640;66641;66642 | chr2:178574794;178574793;178574792 | chr2:179439521;179439520;179439519 |
| N2A | 21212 | 63859;63860;63861 | chr2:178574794;178574793;178574792 | chr2:179439521;179439520;179439519 |
| N2B | 14715 | 44368;44369;44370 | chr2:178574794;178574793;178574792 | chr2:179439521;179439520;179439519 |
| Novex-1 | 14840 | 44743;44744;44745 | chr2:178574794;178574793;178574792 | chr2:179439521;179439520;179439519 |
| Novex-2 | 14907 | 44944;44945;44946 | chr2:178574794;178574793;178574792 | chr2:179439521;179439520;179439519 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs375718660  |
-0.231 | 0.999 | N | 0.478 | 0.434 | None | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.99E-06 | 0 |
| T/A | rs375718660 |
-0.231 | 0.999 | N | 0.478 | 0.434 | None | gnomAD-4.0.0 | 1.36992E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.80046E-06 | 0 | 0 |
| T/I | rs757622611 |
0.104 | 1.0 | N | 0.639 | 0.484 | 0.522559126029 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.99E-06 | 0 |
| T/I | rs757622611 |
0.104 | 1.0 | N | 0.639 | 0.484 | 0.522559126029 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| T/I | rs757622611 |
0.104 | 1.0 | N | 0.639 | 0.484 | 0.522559126029 | gnomAD-4.0.0 | 2.03013E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.40995E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1248 | likely_benign | 0.1393 | benign | -0.396 | Destabilizing | 0.999 | D | 0.478 | neutral | N | 0.47776833 | None | None | I |
| T/C | 0.7318 | likely_pathogenic | 0.7465 | pathogenic | -0.217 | Destabilizing | 1.0 | D | 0.589 | neutral | None | None | None | None | I |
| T/D | 0.8693 | likely_pathogenic | 0.8862 | pathogenic | 0.155 | Stabilizing | 1.0 | D | 0.647 | neutral | None | None | None | None | I |
| T/E | 0.875 | likely_pathogenic | 0.8871 | pathogenic | 0.077 | Stabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | I |
| T/F | 0.7409 | likely_pathogenic | 0.7695 | pathogenic | -0.881 | Destabilizing | 1.0 | D | 0.648 | neutral | None | None | None | None | I |
| T/G | 0.3948 | ambiguous | 0.435 | ambiguous | -0.528 | Destabilizing | 1.0 | D | 0.621 | neutral | None | None | None | None | I |
| T/H | 0.6842 | likely_pathogenic | 0.6982 | pathogenic | -0.804 | Destabilizing | 1.0 | D | 0.614 | neutral | None | None | None | None | I |
| T/I | 0.7122 | likely_pathogenic | 0.7539 | pathogenic | -0.169 | Destabilizing | 1.0 | D | 0.639 | neutral | N | 0.50878467 | None | None | I |
| T/K | 0.7852 | likely_pathogenic | 0.8141 | pathogenic | -0.348 | Destabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | I |
| T/L | 0.2811 | likely_benign | 0.3545 | ambiguous | -0.169 | Destabilizing | 0.999 | D | 0.608 | neutral | None | None | None | None | I |
| T/M | 0.1698 | likely_benign | 0.1882 | benign | 0.056 | Stabilizing | 1.0 | D | 0.597 | neutral | None | None | None | None | I |
| T/N | 0.3043 | likely_benign | 0.3437 | ambiguous | -0.119 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | N | 0.438596653 | None | None | I |
| T/P | 0.5138 | ambiguous | 0.5547 | ambiguous | -0.216 | Destabilizing | 1.0 | D | 0.627 | neutral | N | 0.483440721 | None | None | I |
| T/Q | 0.6519 | likely_pathogenic | 0.6674 | pathogenic | -0.366 | Destabilizing | 1.0 | D | 0.646 | neutral | None | None | None | None | I |
| T/R | 0.7411 | likely_pathogenic | 0.753 | pathogenic | -0.049 | Destabilizing | 1.0 | D | 0.628 | neutral | None | None | None | None | I |
| T/S | 0.2017 | likely_benign | 0.2182 | benign | -0.343 | Destabilizing | 0.999 | D | 0.503 | neutral | N | 0.424509848 | None | None | I |
| T/V | 0.4463 | ambiguous | 0.4805 | ambiguous | -0.216 | Destabilizing | 0.999 | D | 0.574 | neutral | None | None | None | None | I |
| T/W | 0.9354 | likely_pathogenic | 0.939 | pathogenic | -0.872 | Destabilizing | 1.0 | D | 0.656 | neutral | None | None | None | None | I |
| T/Y | 0.7667 | likely_pathogenic | 0.7843 | pathogenic | -0.595 | Destabilizing | 1.0 | D | 0.634 | 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.