Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31348 | 94267;94268;94269 | chr2:178547584;178547583;178547582 | chr2:179412311;179412310;179412309 |
| N2AB | 29707 | 89344;89345;89346 | chr2:178547584;178547583;178547582 | chr2:179412311;179412310;179412309 |
| N2A | 28780 | 86563;86564;86565 | chr2:178547584;178547583;178547582 | chr2:179412311;179412310;179412309 |
| N2B | 22283 | 67072;67073;67074 | chr2:178547584;178547583;178547582 | chr2:179412311;179412310;179412309 |
| Novex-1 | 22408 | 67447;67448;67449 | chr2:178547584;178547583;178547582 | chr2:179412311;179412310;179412309 |
| Novex-2 | 22475 | 67648;67649;67650 | chr2:178547584;178547583;178547582 | chr2:179412311;179412310;179412309 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/M | rs769112668  |
-1.269 | 1.0 | N | 0.825 | 0.41 | 0.366085729538 | gnomAD-2.1.1 | 7.24E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 5.88197E-04 | None | 0 | 0 | 0 |
| K/M | rs769112668 |
-1.269 | 1.0 | N | 0.825 | 0.41 | 0.366085729538 | gnomAD-4.0.0 | 2.80516E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 4.40539E-04 | 4.96936E-05 |
| K/N | rs1450962474 |
-1.933 | 0.993 | D | 0.796 | 0.32 | 0.298056030225 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| K/Q | rs776880399 |
-1.262 | 0.993 | N | 0.793 | 0.432 | 0.31291088546 | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| K/Q | rs776880399 |
-1.262 | 0.993 | N | 0.793 | 0.432 | 0.31291088546 | gnomAD-4.0.0 | 1.59111E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85798E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.959 | likely_pathogenic | 0.9337 | pathogenic | -1.39 | Destabilizing | 0.983 | D | 0.732 | prob.delet. | None | None | None | None | N |
| K/C | 0.9046 | likely_pathogenic | 0.8521 | pathogenic | -1.344 | Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | N |
| K/D | 0.9969 | likely_pathogenic | 0.9957 | pathogenic | -1.94 | Destabilizing | 0.998 | D | 0.822 | deleterious | None | None | None | None | N |
| K/E | 0.9147 | likely_pathogenic | 0.8793 | pathogenic | -1.612 | Destabilizing | 0.977 | D | 0.673 | neutral | N | 0.511046788 | None | None | N |
| K/F | 0.9742 | likely_pathogenic | 0.9579 | pathogenic | -0.65 | Destabilizing | 1.0 | D | 0.88 | deleterious | None | None | None | None | N |
| K/G | 0.9763 | likely_pathogenic | 0.9599 | pathogenic | -1.885 | Destabilizing | 0.998 | D | 0.787 | deleterious | None | None | None | None | N |
| K/H | 0.8106 | likely_pathogenic | 0.737 | pathogenic | -1.618 | Destabilizing | 0.999 | D | 0.834 | deleterious | None | None | None | None | N |
| K/I | 0.8579 | likely_pathogenic | 0.8188 | pathogenic | 0.028 | Stabilizing | 0.998 | D | 0.89 | deleterious | None | None | None | None | N |
| K/L | 0.7979 | likely_pathogenic | 0.7695 | pathogenic | 0.028 | Stabilizing | 0.995 | D | 0.787 | deleterious | None | None | None | None | N |
| K/M | 0.555 | ambiguous | 0.5107 | ambiguous | -0.392 | Destabilizing | 1.0 | D | 0.825 | deleterious | N | 0.507552519 | None | None | N |
| K/N | 0.9822 | likely_pathogenic | 0.9735 | pathogenic | -1.763 | Destabilizing | 0.993 | D | 0.796 | deleterious | D | 0.522403093 | None | None | N |
| K/P | 0.9994 | likely_pathogenic | 0.9993 | pathogenic | -0.427 | Destabilizing | 0.999 | D | 0.841 | deleterious | None | None | None | None | N |
| K/Q | 0.5049 | ambiguous | 0.4037 | ambiguous | -1.355 | Destabilizing | 0.993 | D | 0.793 | deleterious | N | 0.483067485 | None | None | N |
| K/R | 0.1527 | likely_benign | 0.1281 | benign | -0.722 | Destabilizing | 0.235 | N | 0.398 | neutral | N | 0.507032444 | None | None | N |
| K/S | 0.9749 | likely_pathogenic | 0.9529 | pathogenic | -2.271 | Highly Destabilizing | 0.983 | D | 0.702 | prob.neutral | None | None | None | None | N |
| K/T | 0.9056 | likely_pathogenic | 0.8543 | pathogenic | -1.673 | Destabilizing | 0.997 | D | 0.809 | deleterious | N | 0.48509172 | None | None | N |
| K/V | 0.8397 | likely_pathogenic | 0.7968 | pathogenic | -0.427 | Destabilizing | 0.998 | D | 0.825 | deleterious | None | None | None | None | N |
| K/W | 0.9563 | likely_pathogenic | 0.9339 | pathogenic | -0.701 | Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| K/Y | 0.9041 | likely_pathogenic | 0.8578 | pathogenic | -0.338 | Destabilizing | 0.999 | D | 0.879 | 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.