Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23074 | 69445;69446;69447 | chr2:178577115;178577114;178577113 | chr2:179441842;179441841;179441840 |
| N2AB | 21433 | 64522;64523;64524 | chr2:178577115;178577114;178577113 | chr2:179441842;179441841;179441840 |
| N2A | 20506 | 61741;61742;61743 | chr2:178577115;178577114;178577113 | chr2:179441842;179441841;179441840 |
| N2B | 14009 | 42250;42251;42252 | chr2:178577115;178577114;178577113 | chr2:179441842;179441841;179441840 |
| Novex-1 | 14134 | 42625;42626;42627 | chr2:178577115;178577114;178577113 | chr2:179441842;179441841;179441840 |
| Novex-2 | 14201 | 42826;42827;42828 | chr2:178577115;178577114;178577113 | chr2:179441842;179441841;179441840 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/Y | rs1485952946  |
-0.393 | 0.667 | N | 0.716 | 0.263 | 0.542007956216 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| S/Y | rs1485952946 |
-0.393 | 0.667 | N | 0.716 | 0.263 | 0.542007956216 | gnomAD-4.0.0 | 1.36878E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79928E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0825 | likely_benign | 0.1005 | benign | -0.79 | Destabilizing | 0.001 | N | 0.308 | neutral | N | 0.486619886 | None | None | N |
| S/C | 0.0714 | likely_benign | 0.0796 | benign | -0.603 | Destabilizing | 0.883 | D | 0.638 | neutral | N | 0.50534172 | None | None | N |
| S/D | 0.4497 | ambiguous | 0.5104 | ambiguous | -1.06 | Destabilizing | 0.157 | N | 0.511 | neutral | None | None | None | None | N |
| S/E | 0.5722 | likely_pathogenic | 0.6436 | pathogenic | -0.935 | Destabilizing | 0.272 | N | 0.51 | neutral | None | None | None | None | N |
| S/F | 0.1514 | likely_benign | 0.2033 | benign | -0.58 | Destabilizing | 0.667 | D | 0.721 | prob.delet. | N | 0.507419233 | None | None | N |
| S/G | 0.0693 | likely_benign | 0.0701 | benign | -1.144 | Destabilizing | 0.072 | N | 0.514 | neutral | None | None | None | None | N |
| S/H | 0.1929 | likely_benign | 0.2213 | benign | -1.5 | Destabilizing | 0.909 | D | 0.649 | neutral | None | None | None | None | N |
| S/I | 0.3772 | ambiguous | 0.4793 | ambiguous | 0.085 | Stabilizing | 0.567 | D | 0.705 | prob.neutral | None | None | None | None | N |
| S/K | 0.6083 | likely_pathogenic | 0.6648 | pathogenic | -0.569 | Destabilizing | 0.272 | N | 0.519 | neutral | None | None | None | None | N |
| S/L | 0.1562 | likely_benign | 0.2008 | benign | 0.085 | Stabilizing | 0.157 | N | 0.627 | neutral | None | None | None | None | N |
| S/M | 0.2107 | likely_benign | 0.2605 | benign | 0.079 | Stabilizing | 0.909 | D | 0.643 | neutral | None | None | None | None | N |
| S/N | 0.1181 | likely_benign | 0.1198 | benign | -0.95 | Destabilizing | 0.001 | N | 0.409 | neutral | None | None | None | None | N |
| S/P | 0.9638 | likely_pathogenic | 0.978 | pathogenic | -0.171 | Destabilizing | 0.497 | N | 0.673 | neutral | N | 0.494552376 | None | None | N |
| S/Q | 0.4399 | ambiguous | 0.4958 | ambiguous | -0.862 | Destabilizing | 0.567 | D | 0.513 | neutral | None | None | None | None | N |
| S/R | 0.5189 | ambiguous | 0.5746 | pathogenic | -0.743 | Destabilizing | 0.567 | D | 0.667 | neutral | None | None | None | None | N |
| S/T | 0.1131 | likely_benign | 0.1296 | benign | -0.738 | Destabilizing | 0.124 | N | 0.51 | neutral | N | 0.483118221 | None | None | N |
| S/V | 0.3118 | likely_benign | 0.4068 | ambiguous | -0.171 | Destabilizing | 0.396 | N | 0.638 | neutral | None | None | None | None | N |
| S/W | 0.2627 | likely_benign | 0.3436 | ambiguous | -0.732 | Destabilizing | 0.968 | D | 0.707 | prob.neutral | None | None | None | None | N |
| S/Y | 0.095 | likely_benign | 0.1229 | benign | -0.363 | Destabilizing | 0.667 | D | 0.716 | prob.delet. | N | 0.421243043 | 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.