Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24196 | 72811;72812;72813 | chr2:178573546;178573545;178573544 | chr2:179438273;179438272;179438271 |
| N2AB | 22555 | 67888;67889;67890 | chr2:178573546;178573545;178573544 | chr2:179438273;179438272;179438271 |
| N2A | 21628 | 65107;65108;65109 | chr2:178573546;178573545;178573544 | chr2:179438273;179438272;179438271 |
| N2B | 15131 | 45616;45617;45618 | chr2:178573546;178573545;178573544 | chr2:179438273;179438272;179438271 |
| Novex-1 | 15256 | 45991;45992;45993 | chr2:178573546;178573545;178573544 | chr2:179438273;179438272;179438271 |
| Novex-2 | 15323 | 46192;46193;46194 | chr2:178573546;178573545;178573544 | chr2:179438273;179438272;179438271 |
| 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/C | rs185626486  |
-1.536 | 1.0 | D | 0.823 | 0.558 | None | gnomAD-2.1.1 | 1.16182E-04 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.18454E-03 | None | 0 | None | 0 | 4.05E-05 | 0 |
| R/C | rs185626486 |
-1.536 | 1.0 | D | 0.823 | 0.558 | None | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.16279E-03 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/C | rs185626486 |
-1.536 | 1.0 | D | 0.823 | 0.558 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 2E-03 | 0 | None | None | None | 0 | None |
| R/C | rs185626486 |
-1.536 | 1.0 | D | 0.823 | 0.558 | None | gnomAD-4.0.0 | 3.81081E-05 | None | None | None | None | N | None | 0 | 2.44547E-05 | None | 0 | 5.56483E-04 | None | 0 | 3.60101E-04 | 1.95528E-05 | 7.32751E-05 | 5.22575E-05 |
| R/H | rs200317412 |
-2.089 | 1.0 | D | 0.817 | 0.492 | None | gnomAD-2.1.1 | 2.72284E-04 | None | None | None | None | N | None | 2.26363E-03 | 5.43E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 2.10526E-04 |
| R/H | rs200317412 |
-2.089 | 1.0 | D | 0.817 | 0.492 | None | gnomAD-3.1.2 | 5.78818E-04 | None | None | None | None | N | None | 2.07599E-03 | 1.31113E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/H | rs200317412 |
-2.089 | 1.0 | D | 0.817 | 0.492 | None | 1000 genomes | 7.98722E-04 | None | None | None | None | N | None | 3E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/H | rs200317412 |
-2.089 | 1.0 | D | 0.817 | 0.492 | None | gnomAD-4.0.0 | 1.22977E-04 | None | None | None | None | N | None | 2.1443E-03 | 9.7766E-05 | None | 0 | 0 | None | 0 | 0 | 1.3329E-05 | 1.4619E-05 | 1.91598E-04 |
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 | 0.9145 | likely_pathogenic | 0.94 | pathogenic | -1.578 | Destabilizing | 0.999 | D | 0.636 | neutral | None | None | None | None | N |
| R/C | 0.381 | ambiguous | 0.3978 | ambiguous | -1.597 | Destabilizing | 1.0 | D | 0.823 | deleterious | D | 0.545843855 | None | None | N |
| R/D | 0.9907 | likely_pathogenic | 0.9937 | pathogenic | -1.065 | Destabilizing | 1.0 | D | 0.814 | deleterious | None | None | None | None | N |
| R/E | 0.8991 | likely_pathogenic | 0.923 | pathogenic | -0.846 | Destabilizing | 0.999 | D | 0.681 | prob.neutral | None | None | None | None | N |
| R/F | 0.9683 | likely_pathogenic | 0.9815 | pathogenic | -0.587 | Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | N |
| R/G | 0.8987 | likely_pathogenic | 0.9336 | pathogenic | -1.928 | Destabilizing | 1.0 | D | 0.751 | deleterious | D | 0.552173731 | None | None | N |
| R/H | 0.3217 | likely_benign | 0.4343 | ambiguous | -1.715 | Destabilizing | 1.0 | D | 0.817 | deleterious | D | 0.563783526 | None | None | N |
| R/I | 0.8722 | likely_pathogenic | 0.9142 | pathogenic | -0.566 | Destabilizing | 1.0 | D | 0.852 | deleterious | None | None | None | None | N |
| R/K | 0.3696 | ambiguous | 0.4894 | ambiguous | -1.192 | Destabilizing | 0.998 | D | 0.663 | neutral | None | None | None | None | N |
| R/L | 0.7985 | likely_pathogenic | 0.8714 | pathogenic | -0.566 | Destabilizing | 1.0 | D | 0.751 | deleterious | D | 0.52971461 | None | None | N |
| R/M | 0.8419 | likely_pathogenic | 0.9023 | pathogenic | -1.112 | Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | N |
| R/N | 0.9662 | likely_pathogenic | 0.9754 | pathogenic | -1.389 | Destabilizing | 1.0 | D | 0.774 | deleterious | None | None | None | None | N |
| R/P | 0.9982 | likely_pathogenic | 0.9987 | pathogenic | -0.892 | Destabilizing | 1.0 | D | 0.829 | deleterious | D | 0.564037015 | None | None | N |
| R/Q | 0.2529 | likely_benign | 0.3285 | benign | -1.107 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | N |
| R/S | 0.9223 | likely_pathogenic | 0.9472 | pathogenic | -2.065 | Highly Destabilizing | 1.0 | D | 0.74 | deleterious | N | 0.512669857 | None | None | N |
| R/T | 0.8747 | likely_pathogenic | 0.9227 | pathogenic | -1.646 | Destabilizing | 1.0 | D | 0.746 | deleterious | None | None | None | None | N |
| R/V | 0.8877 | likely_pathogenic | 0.9221 | pathogenic | -0.892 | Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | N |
| R/W | 0.6778 | likely_pathogenic | 0.7958 | pathogenic | -0.258 | Destabilizing | 1.0 | D | 0.806 | deleterious | None | None | None | None | N |
| R/Y | 0.899 | likely_pathogenic | 0.938 | pathogenic | -0.113 | Destabilizing | 1.0 | D | 0.851 | 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.