Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25711 | 77356;77357;77358 | chr2:178569001;178569000;178568999 | chr2:179433728;179433727;179433726 |
| N2AB | 24070 | 72433;72434;72435 | chr2:178569001;178569000;178568999 | chr2:179433728;179433727;179433726 |
| N2A | 23143 | 69652;69653;69654 | chr2:178569001;178569000;178568999 | chr2:179433728;179433727;179433726 |
| N2B | 16646 | 50161;50162;50163 | chr2:178569001;178569000;178568999 | chr2:179433728;179433727;179433726 |
| Novex-1 | 16771 | 50536;50537;50538 | chr2:178569001;178569000;178568999 | chr2:179433728;179433727;179433726 |
| Novex-2 | 16838 | 50737;50738;50739 | chr2:178569001;178569000;178568999 | chr2:179433728;179433727;179433726 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs887610262  |
-0.838 | 0.386 | N | 0.45 | 0.427 | 0.201204373187 | 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 |
| T/A | rs887610262 |
-0.838 | 0.386 | N | 0.45 | 0.427 | 0.201204373187 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| T/A | rs887610262 |
-0.838 | 0.386 | N | 0.45 | 0.427 | 0.201204373187 | gnomAD-4.0.0 | 6.09028E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.02504E-06 | 0 | 3.40275E-05 |
| T/I | None | None | 0.997 | N | 0.673 | 0.472 | 0.518585293439 | gnomAD-4.0.0 | 1.20033E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.66327E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.4903 | ambiguous | 0.4347 | ambiguous | -0.582 | Destabilizing | 0.386 | N | 0.45 | neutral | N | 0.489605306 | None | None | N |
| T/C | 0.852 | likely_pathogenic | 0.8406 | pathogenic | -0.677 | Destabilizing | 1.0 | D | 0.633 | neutral | None | None | None | None | N |
| T/D | 0.8099 | likely_pathogenic | 0.7637 | pathogenic | -1.531 | Destabilizing | 0.978 | D | 0.614 | neutral | None | None | None | None | N |
| T/E | 0.8753 | likely_pathogenic | 0.8492 | pathogenic | -1.523 | Destabilizing | 0.993 | D | 0.616 | neutral | None | None | None | None | N |
| T/F | 0.8846 | likely_pathogenic | 0.8555 | pathogenic | -0.897 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| T/G | 0.4624 | ambiguous | 0.4221 | ambiguous | -0.809 | Destabilizing | 0.991 | D | 0.531 | neutral | None | None | None | None | N |
| T/H | 0.6999 | likely_pathogenic | 0.6828 | pathogenic | -1.223 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | N |
| T/I | 0.9432 | likely_pathogenic | 0.9229 | pathogenic | -0.069 | Destabilizing | 0.997 | D | 0.673 | neutral | N | 0.514572869 | None | None | N |
| T/K | 0.7267 | likely_pathogenic | 0.6683 | pathogenic | -0.76 | Destabilizing | 0.995 | D | 0.621 | neutral | None | None | None | None | N |
| T/L | 0.5726 | likely_pathogenic | 0.4956 | ambiguous | -0.069 | Destabilizing | 0.992 | D | 0.553 | neutral | None | None | None | None | N |
| T/M | 0.4133 | ambiguous | 0.3512 | ambiguous | 0.33 | Stabilizing | 1.0 | D | 0.639 | neutral | None | None | None | None | N |
| T/N | 0.3701 | ambiguous | 0.336 | benign | -1.014 | Destabilizing | 0.971 | D | 0.615 | neutral | N | 0.474562016 | None | None | N |
| T/P | 0.9252 | likely_pathogenic | 0.8895 | pathogenic | -0.21 | Destabilizing | 0.985 | D | 0.67 | neutral | D | 0.529550026 | None | None | N |
| T/Q | 0.6593 | likely_pathogenic | 0.6147 | pathogenic | -1.305 | Destabilizing | 0.995 | D | 0.667 | neutral | None | None | None | None | N |
| T/R | 0.6912 | likely_pathogenic | 0.6243 | pathogenic | -0.436 | Destabilizing | 0.999 | D | 0.677 | prob.neutral | None | None | None | None | N |
| T/S | 0.1745 | likely_benign | 0.1617 | benign | -1.05 | Destabilizing | 0.106 | N | 0.221 | neutral | N | 0.490737627 | None | None | N |
| T/V | 0.8519 | likely_pathogenic | 0.8211 | pathogenic | -0.21 | Destabilizing | 0.988 | D | 0.519 | neutral | None | None | None | None | N |
| T/W | 0.9665 | likely_pathogenic | 0.9572 | pathogenic | -0.942 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | N |
| T/Y | 0.8719 | likely_pathogenic | 0.8439 | pathogenic | -0.592 | Destabilizing | 1.0 | D | 0.705 | 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.