Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23098 | 69517;69518;69519 | chr2:178577043;178577042;178577041 | chr2:179441770;179441769;179441768 |
| N2AB | 21457 | 64594;64595;64596 | chr2:178577043;178577042;178577041 | chr2:179441770;179441769;179441768 |
| N2A | 20530 | 61813;61814;61815 | chr2:178577043;178577042;178577041 | chr2:179441770;179441769;179441768 |
| N2B | 14033 | 42322;42323;42324 | chr2:178577043;178577042;178577041 | chr2:179441770;179441769;179441768 |
| Novex-1 | 14158 | 42697;42698;42699 | chr2:178577043;178577042;178577041 | chr2:179441770;179441769;179441768 |
| Novex-2 | 14225 | 42898;42899;42900 | chr2:178577043;178577042;178577041 | chr2:179441770;179441769;179441768 |
| 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/K | rs771768640  |
-0.125 | 0.987 | N | 0.56 | 0.297 | 0.223146558224 | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | N | None | 8.27E-05 | 2.83E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/K | rs771768640 |
-0.125 | 0.987 | N | 0.56 | 0.297 | 0.223146558224 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/K | rs771768640 |
-0.125 | 0.987 | N | 0.56 | 0.297 | 0.223146558224 | gnomAD-4.0.0 | 3.71908E-06 | None | None | None | None | N | None | 6.67824E-05 | 1.66767E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.4986 | ambiguous | 0.4652 | ambiguous | -0.434 | Destabilizing | 0.992 | D | 0.56 | neutral | None | None | None | None | N |
| R/C | 0.1408 | likely_benign | 0.141 | benign | -0.52 | Destabilizing | 1.0 | D | 0.67 | neutral | None | None | None | None | N |
| R/D | 0.7066 | likely_pathogenic | 0.7032 | pathogenic | 0.084 | Stabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | N |
| R/E | 0.4037 | ambiguous | 0.3957 | ambiguous | 0.208 | Stabilizing | 0.999 | D | 0.627 | neutral | None | None | None | None | N |
| R/F | 0.5111 | ambiguous | 0.5025 | ambiguous | -0.335 | Destabilizing | 0.998 | D | 0.674 | neutral | None | None | None | None | N |
| R/G | 0.3324 | likely_benign | 0.3003 | benign | -0.721 | Destabilizing | 0.994 | D | 0.583 | neutral | N | 0.509862105 | None | None | N |
| R/H | 0.0758 | likely_benign | 0.0794 | benign | -1.079 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| R/I | 0.3356 | likely_benign | 0.3098 | benign | 0.32 | Stabilizing | 0.995 | D | 0.66 | neutral | None | None | None | None | N |
| R/K | 0.1142 | likely_benign | 0.1099 | benign | -0.386 | Destabilizing | 0.987 | D | 0.56 | neutral | N | 0.46489782 | None | None | N |
| R/L | 0.2868 | likely_benign | 0.2763 | benign | 0.32 | Stabilizing | 0.983 | D | 0.553 | neutral | None | None | None | None | N |
| R/M | 0.3451 | ambiguous | 0.3216 | benign | -0.19 | Destabilizing | 0.948 | D | 0.493 | neutral | N | 0.457761204 | None | None | N |
| R/N | 0.5651 | likely_pathogenic | 0.5505 | ambiguous | -0.095 | Destabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | N |
| R/P | 0.9101 | likely_pathogenic | 0.89 | pathogenic | 0.09 | Stabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | N |
| R/Q | 0.0936 | likely_benign | 0.0907 | benign | -0.174 | Destabilizing | 0.999 | D | 0.675 | neutral | None | None | None | None | N |
| R/S | 0.4435 | ambiguous | 0.415 | ambiguous | -0.717 | Destabilizing | 0.994 | D | 0.623 | neutral | N | 0.369848644 | None | None | N |
| R/T | 0.2541 | likely_benign | 0.2313 | benign | -0.414 | Destabilizing | 0.994 | D | 0.632 | neutral | N | 0.382548582 | None | None | N |
| R/V | 0.3897 | ambiguous | 0.38 | ambiguous | 0.09 | Stabilizing | 0.983 | D | 0.601 | neutral | None | None | None | None | N |
| R/W | 0.1721 | likely_benign | 0.1636 | benign | -0.142 | Destabilizing | 1.0 | D | 0.657 | neutral | N | 0.48147455 | None | None | N |
| R/Y | 0.3355 | likely_benign | 0.336 | benign | 0.19 | Stabilizing | 1.0 | D | 0.677 | prob.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.