Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30801 | 92626;92627;92628 | chr2:178549225;178549224;178549223 | chr2:179413952;179413951;179413950 |
| N2AB | 29160 | 87703;87704;87705 | chr2:178549225;178549224;178549223 | chr2:179413952;179413951;179413950 |
| N2A | 28233 | 84922;84923;84924 | chr2:178549225;178549224;178549223 | chr2:179413952;179413951;179413950 |
| N2B | 21736 | 65431;65432;65433 | chr2:178549225;178549224;178549223 | chr2:179413952;179413951;179413950 |
| Novex-1 | 21861 | 65806;65807;65808 | chr2:178549225;178549224;178549223 | chr2:179413952;179413951;179413950 |
| Novex-2 | 21928 | 66007;66008;66009 | chr2:178549225;178549224;178549223 | chr2:179413952;179413951;179413950 |
| 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/E | None | None | 0.997 | N | 0.781 | 0.421 | 0.461934685604 | gnomAD-4.0.0 | 6.84204E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65656E-05 |
| A/G | None | None | 0.117 | N | 0.437 | 0.24 | 0.199424873507 | gnomAD-4.0.0 | 1.36841E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79887E-06 | 0 | 0 |
| A/V | rs372570504  |
-0.042 | 0.989 | N | 0.75 | 0.25 | None | gnomAD-2.1.1 | 3.21E-05 | None | None | None | None | I | None | 3.72024E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| A/V | rs372570504 |
-0.042 | 0.989 | N | 0.75 | 0.25 | None | gnomAD-3.1.2 | 1.05143E-04 | None | None | None | None | I | None | 3.8597E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/V | rs372570504 |
-0.042 | 0.989 | N | 0.75 | 0.25 | None | gnomAD-4.0.0 | 2.5407E-05 | None | None | None | None | I | None | 5.47265E-04 | 0 | None | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.7459 | likely_pathogenic | 0.6891 | pathogenic | -0.89 | Destabilizing | 1.0 | D | 0.78 | deleterious | None | None | None | None | I |
| A/D | 0.9599 | likely_pathogenic | 0.9466 | pathogenic | -0.77 | Destabilizing | 0.998 | D | 0.825 | deleterious | None | None | None | None | I |
| A/E | 0.8904 | likely_pathogenic | 0.8744 | pathogenic | -0.933 | Destabilizing | 0.997 | D | 0.781 | deleterious | N | 0.490865391 | None | None | I |
| A/F | 0.7717 | likely_pathogenic | 0.6766 | pathogenic | -0.991 | Destabilizing | 0.999 | D | 0.861 | deleterious | None | None | None | None | I |
| A/G | 0.4284 | ambiguous | 0.3302 | benign | -0.372 | Destabilizing | 0.117 | N | 0.437 | neutral | N | 0.483863952 | None | None | I |
| A/H | 0.923 | likely_pathogenic | 0.8921 | pathogenic | -0.295 | Destabilizing | 1.0 | D | 0.849 | deleterious | None | None | None | None | I |
| A/I | 0.5385 | ambiguous | 0.5593 | ambiguous | -0.488 | Destabilizing | 0.999 | D | 0.785 | deleterious | None | None | None | None | I |
| A/K | 0.9422 | likely_pathogenic | 0.9244 | pathogenic | -0.725 | Destabilizing | 0.998 | D | 0.781 | deleterious | None | None | None | None | I |
| A/L | 0.6026 | likely_pathogenic | 0.5814 | pathogenic | -0.488 | Destabilizing | 0.998 | D | 0.743 | deleterious | None | None | None | None | I |
| A/M | 0.6211 | likely_pathogenic | 0.5958 | pathogenic | -0.531 | Destabilizing | 1.0 | D | 0.782 | deleterious | None | None | None | None | I |
| A/N | 0.8788 | likely_pathogenic | 0.8416 | pathogenic | -0.445 | Destabilizing | 0.995 | D | 0.832 | deleterious | None | None | None | None | I |
| A/P | 0.9607 | likely_pathogenic | 0.955 | pathogenic | -0.412 | Destabilizing | 0.999 | D | 0.785 | deleterious | D | 0.545991532 | None | None | I |
| A/Q | 0.8517 | likely_pathogenic | 0.8189 | pathogenic | -0.765 | Destabilizing | 0.999 | D | 0.797 | deleterious | None | None | None | None | I |
| A/R | 0.8629 | likely_pathogenic | 0.8258 | pathogenic | -0.168 | Destabilizing | 0.998 | D | 0.785 | deleterious | None | None | None | None | I |
| A/S | 0.2478 | likely_benign | 0.2169 | benign | -0.603 | Destabilizing | 0.977 | D | 0.584 | neutral | N | 0.481283513 | None | None | I |
| A/T | 0.4329 | ambiguous | 0.3904 | ambiguous | -0.695 | Destabilizing | 0.997 | D | 0.77 | deleterious | N | 0.495602333 | None | None | I |
| A/V | 0.2712 | likely_benign | 0.2734 | benign | -0.412 | Destabilizing | 0.989 | D | 0.75 | deleterious | N | 0.496431448 | None | None | I |
| A/W | 0.9732 | likely_pathogenic | 0.9542 | pathogenic | -1.081 | Destabilizing | 1.0 | D | 0.848 | deleterious | None | None | None | None | I |
| A/Y | 0.9079 | likely_pathogenic | 0.8578 | pathogenic | -0.768 | Destabilizing | 1.0 | D | 0.855 | deleterious | 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.