Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31702 | 95329;95330;95331 | chr2:178546227;178546226;178546225 | chr2:179410954;179410953;179410952 |
| N2AB | 30061 | 90406;90407;90408 | chr2:178546227;178546226;178546225 | chr2:179410954;179410953;179410952 |
| N2A | 29134 | 87625;87626;87627 | chr2:178546227;178546226;178546225 | chr2:179410954;179410953;179410952 |
| N2B | 22637 | 68134;68135;68136 | chr2:178546227;178546226;178546225 | chr2:179410954;179410953;179410952 |
| Novex-1 | 22762 | 68509;68510;68511 | chr2:178546227;178546226;178546225 | chr2:179410954;179410953;179410952 |
| Novex-2 | 22829 | 68710;68711;68712 | chr2:178546227;178546226;178546225 | chr2:179410954;179410953;179410952 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | None | None | None | N | 0.083 | 0.126 | 0.418718287753 | gnomAD-4.0.0 | 2.05814E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.705E-06 | 0 | 0 |
| M/L | rs370696758  |
-0.234 | None | N | 0.081 | 0.14 | 0.36893422563 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.94E-06 | 0 |
| M/L | rs370696758 |
-0.234 | None | N | 0.081 | 0.14 | 0.36893422563 | 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 |
| M/L | rs370696758 |
-0.234 | None | N | 0.081 | 0.14 | 0.36893422563 | gnomAD-4.0.0 | 1.86259E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.54752E-06 | 0 | 0 |
| M/T | rs778808720 |
-0.512 | None | N | 0.157 | 0.118 | 0.538974603628 | gnomAD-2.1.1 | 8.1E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.79E-05 | 0 |
| M/T | rs778808720 |
-0.512 | None | N | 0.157 | 0.118 | 0.538974603628 | 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 |
| M/T | rs778808720 |
-0.512 | None | N | 0.157 | 0.118 | 0.538974603628 | gnomAD-4.0.0 | 3.10482E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.24663E-06 | 0 | 0 |
| M/V | rs370696758 |
-0.521 | None | N | 0.097 | 0.112 | 0.469742815239 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.31E-05 | None | 0 | 0 | 0 |
| M/V | rs370696758 |
-0.521 | None | N | 0.097 | 0.112 | 0.469742815239 | gnomAD-4.0.0 | 4.11398E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.50618E-06 | 1.16404E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.1242 | likely_benign | 0.1554 | benign | -1.36 | Destabilizing | 0.001 | N | 0.215 | neutral | None | None | None | None | N |
| M/C | 0.4664 | ambiguous | 0.5791 | pathogenic | -1.181 | Destabilizing | 0.132 | N | 0.529 | neutral | None | None | None | None | N |
| M/D | 0.3484 | ambiguous | 0.4173 | ambiguous | -0.156 | Destabilizing | 0.002 | N | 0.403 | neutral | None | None | None | None | N |
| M/E | 0.2296 | likely_benign | 0.2919 | benign | -0.109 | Destabilizing | 0.002 | N | 0.344 | neutral | None | None | None | None | N |
| M/F | 0.1828 | likely_benign | 0.2471 | benign | -0.301 | Destabilizing | 0.004 | N | 0.417 | neutral | None | None | None | None | N |
| M/G | 0.2994 | likely_benign | 0.3741 | ambiguous | -1.691 | Destabilizing | 0.004 | N | 0.367 | neutral | None | None | None | None | N |
| M/H | 0.2053 | likely_benign | 0.2743 | benign | -0.802 | Destabilizing | 0.132 | N | 0.605 | neutral | None | None | None | None | N |
| M/I | 0.1056 | likely_benign | 0.1534 | benign | -0.513 | Destabilizing | None | N | 0.083 | neutral | N | 0.434818134 | None | None | N |
| M/K | 0.1235 | likely_benign | 0.1625 | benign | -0.323 | Destabilizing | 0.001 | N | 0.289 | neutral | N | 0.348236513 | None | None | N |
| M/L | 0.0759 | likely_benign | 0.0993 | benign | -0.513 | Destabilizing | None | N | 0.081 | neutral | N | 0.429622958 | None | None | N |
| M/N | 0.1335 | likely_benign | 0.1657 | benign | -0.256 | Destabilizing | None | N | 0.226 | neutral | None | None | None | None | N |
| M/P | 0.3658 | ambiguous | 0.4268 | ambiguous | -0.766 | Destabilizing | 0.018 | N | 0.521 | neutral | None | None | None | None | N |
| M/Q | 0.1433 | likely_benign | 0.1819 | benign | -0.277 | Destabilizing | None | N | 0.127 | neutral | None | None | None | None | N |
| M/R | 0.136 | likely_benign | 0.1698 | benign | 0.05 | Stabilizing | 0.007 | N | 0.447 | neutral | N | 0.374596395 | None | None | N |
| M/S | 0.1331 | likely_benign | 0.166 | benign | -0.893 | Destabilizing | None | N | 0.161 | neutral | None | None | None | None | N |
| M/T | 0.0701 | likely_benign | 0.074 | benign | -0.728 | Destabilizing | None | N | 0.157 | neutral | N | 0.334960571 | None | None | N |
| M/V | 0.0621 | likely_benign | 0.0703 | benign | -0.766 | Destabilizing | None | N | 0.097 | neutral | N | 0.45942579 | None | None | N |
| M/W | 0.3622 | ambiguous | 0.43 | ambiguous | -0.294 | Destabilizing | 0.316 | N | 0.525 | neutral | None | None | None | None | N |
| M/Y | 0.3258 | likely_benign | 0.4125 | ambiguous | -0.27 | Destabilizing | 0.041 | N | 0.564 | neutral | 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.