Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24261 | 73006;73007;73008 | chr2:178573351;178573350;178573349 | chr2:179438078;179438077;179438076 |
| N2AB | 22620 | 68083;68084;68085 | chr2:178573351;178573350;178573349 | chr2:179438078;179438077;179438076 |
| N2A | 21693 | 65302;65303;65304 | chr2:178573351;178573350;178573349 | chr2:179438078;179438077;179438076 |
| N2B | 15196 | 45811;45812;45813 | chr2:178573351;178573350;178573349 | chr2:179438078;179438077;179438076 |
| Novex-1 | 15321 | 46186;46187;46188 | chr2:178573351;178573350;178573349 | chr2:179438078;179438077;179438076 |
| Novex-2 | 15388 | 46387;46388;46389 | chr2:178573351;178573350;178573349 | chr2:179438078;179438077;179438076 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/Q | rs142874389  |
-1.493 | 0.997 | N | 0.699 | 0.333 | None | gnomAD-2.1.1 | 6.74063E-04 | None | None | None | None | N | None | 4.90363E-03 | 3.59511E-04 | None | 0 | 3.39597E-04 | None | 6.18E-05 | None | 4.65E-05 | 1.33017E-04 | 3.68732E-04 |
| R/Q | rs142874389 |
-1.493 | 0.997 | N | 0.699 | 0.333 | None | gnomAD-3.1.2 | 1.31591E-03 | None | None | None | None | N | None | 4.42093E-03 | 6.55652E-04 | 0 | 0 | 0 | None | 0 | 3.16456E-03 | 8.83E-05 | 0 | 0 |
| R/Q | rs142874389 |
-1.493 | 0.997 | N | 0.699 | 0.333 | None | 1000 genomes | 1.39776E-03 | None | None | None | None | N | None | 5.3E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/Q | rs142874389 |
-1.493 | 0.997 | N | 0.699 | 0.333 | None | gnomAD-4.0.0 | 3.25543E-04 | None | None | None | None | N | None | 4.55059E-03 | 4.72163E-04 | None | 0 | 2.27087E-04 | None | 3.26318E-05 | 1.75685E-04 | 9.54429E-05 | 2.60329E-05 | 3.89026E-04 |
| R/W | rs1275789320 |
-0.842 | 1.0 | N | 0.682 | 0.338 | 0.384919354899 | gnomAD-2.1.1 | 5.33E-06 | None | None | None | None | N | None | 6.79E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/W | rs1275789320 |
-0.842 | 1.0 | N | 0.682 | 0.338 | 0.384919354899 | gnomAD-4.0.0 | 9.40199E-06 | None | None | None | None | N | None | 6.46078E-05 | 0 | None | 0 | 5.14562E-05 | None | 0 | 0 | 6.51977E-06 | 1.39353E-05 | 1.75574E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9676 | likely_pathogenic | 0.9417 | pathogenic | -2.167 | Highly Destabilizing | 0.953 | D | 0.693 | prob.neutral | None | None | None | None | N |
| R/C | 0.4951 | ambiguous | 0.4055 | ambiguous | -2.115 | Highly Destabilizing | 0.999 | D | 0.741 | deleterious | None | None | None | None | N |
| R/D | 0.9961 | likely_pathogenic | 0.993 | pathogenic | -1.643 | Destabilizing | 0.986 | D | 0.732 | prob.delet. | None | None | None | None | N |
| R/E | 0.9446 | likely_pathogenic | 0.9137 | pathogenic | -1.384 | Destabilizing | 0.91 | D | 0.69 | prob.neutral | None | None | None | None | N |
| R/F | 0.9462 | likely_pathogenic | 0.921 | pathogenic | -1.191 | Destabilizing | 0.998 | D | 0.769 | deleterious | None | None | None | None | N |
| R/G | 0.9348 | likely_pathogenic | 0.879 | pathogenic | -2.54 | Highly Destabilizing | 0.975 | D | 0.716 | prob.delet. | N | 0.494157074 | None | None | N |
| R/H | 0.4019 | ambiguous | 0.3354 | benign | -1.765 | Destabilizing | 0.998 | D | 0.73 | prob.delet. | None | None | None | None | N |
| R/I | 0.8426 | likely_pathogenic | 0.7783 | pathogenic | -1.054 | Destabilizing | 0.993 | D | 0.769 | deleterious | None | None | None | None | N |
| R/K | 0.1478 | likely_benign | 0.1357 | benign | -1.183 | Destabilizing | 0.06 | N | 0.372 | neutral | None | None | None | None | N |
| R/L | 0.7755 | likely_pathogenic | 0.6918 | pathogenic | -1.054 | Destabilizing | 0.975 | D | 0.716 | prob.delet. | N | 0.478188732 | None | None | N |
| R/M | 0.7537 | likely_pathogenic | 0.6956 | pathogenic | -1.534 | Destabilizing | 0.999 | D | 0.721 | prob.delet. | None | None | None | None | N |
| R/N | 0.9856 | likely_pathogenic | 0.9746 | pathogenic | -1.877 | Destabilizing | 0.986 | D | 0.694 | prob.neutral | None | None | None | None | N |
| R/P | 0.9982 | likely_pathogenic | 0.9971 | pathogenic | -1.418 | Destabilizing | 0.996 | D | 0.746 | deleterious | N | 0.505931453 | None | None | N |
| R/Q | 0.3589 | ambiguous | 0.2873 | benign | -1.639 | Destabilizing | 0.997 | D | 0.699 | prob.neutral | N | 0.479179918 | None | None | N |
| R/S | 0.9792 | likely_pathogenic | 0.9633 | pathogenic | -2.696 | Highly Destabilizing | 0.953 | D | 0.695 | prob.neutral | None | None | None | None | N |
| R/T | 0.9457 | likely_pathogenic | 0.9145 | pathogenic | -2.2 | Highly Destabilizing | 0.986 | D | 0.709 | prob.delet. | None | None | None | None | N |
| R/V | 0.8898 | likely_pathogenic | 0.8438 | pathogenic | -1.418 | Destabilizing | 0.993 | D | 0.759 | deleterious | None | None | None | None | N |
| R/W | 0.6533 | likely_pathogenic | 0.5756 | pathogenic | -0.666 | Destabilizing | 1.0 | D | 0.682 | prob.neutral | N | 0.469567905 | None | None | N |
| R/Y | 0.815 | likely_pathogenic | 0.7775 | pathogenic | -0.621 | Destabilizing | 0.998 | D | 0.753 | 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.