Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19378 | 58357;58358;58359 | chr2:178594362;178594361;178594360 | chr2:179459089;179459088;179459087 |
| N2AB | 17737 | 53434;53435;53436 | chr2:178594362;178594361;178594360 | chr2:179459089;179459088;179459087 |
| N2A | 16810 | 50653;50654;50655 | chr2:178594362;178594361;178594360 | chr2:179459089;179459088;179459087 |
| N2B | 10313 | 31162;31163;31164 | chr2:178594362;178594361;178594360 | chr2:179459089;179459088;179459087 |
| Novex-1 | 10438 | 31537;31538;31539 | chr2:178594362;178594361;178594360 | chr2:179459089;179459088;179459087 |
| Novex-2 | 10505 | 31738;31739;31740 | chr2:178594362;178594361;178594360 | chr2:179459089;179459088;179459087 |
| 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/I | rs371456511  |
-0.225 | 0.999 | N | 0.687 | 0.321 | None | gnomAD-2.1.1 | 8.56E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.27E-06 | 1.76616E-04 |
| T/I | rs371456511 |
-0.225 | 0.999 | N | 0.687 | 0.321 | None | gnomAD-4.0.0 | 6.56955E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.17284E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.147 | likely_benign | 0.1367 | benign | -0.671 | Destabilizing | 0.976 | D | 0.477 | neutral | N | 0.520164818 | None | None | N |
| T/C | 0.5908 | likely_pathogenic | 0.574 | pathogenic | -0.43 | Destabilizing | 1.0 | D | 0.676 | prob.neutral | None | None | None | None | N |
| T/D | 0.7993 | likely_pathogenic | 0.7654 | pathogenic | 0.038 | Stabilizing | 0.995 | D | 0.665 | prob.neutral | None | None | None | None | N |
| T/E | 0.5845 | likely_pathogenic | 0.5364 | ambiguous | 0.006 | Stabilizing | 0.965 | D | 0.547 | neutral | None | None | None | None | N |
| T/F | 0.4433 | ambiguous | 0.3998 | ambiguous | -0.911 | Destabilizing | 0.999 | D | 0.778 | deleterious | None | None | None | None | N |
| T/G | 0.6152 | likely_pathogenic | 0.5853 | pathogenic | -0.882 | Destabilizing | 0.991 | D | 0.61 | neutral | None | None | None | None | N |
| T/H | 0.4743 | ambiguous | 0.4294 | ambiguous | -1.194 | Destabilizing | 0.999 | D | 0.707 | prob.delet. | None | None | None | None | N |
| T/I | 0.1445 | likely_benign | 0.1316 | benign | -0.216 | Destabilizing | 0.999 | D | 0.687 | prob.delet. | N | 0.468986636 | None | None | N |
| T/K | 0.4173 | ambiguous | 0.3607 | ambiguous | -0.596 | Destabilizing | 0.965 | D | 0.676 | prob.neutral | None | None | None | None | N |
| T/L | 0.1386 | likely_benign | 0.1275 | benign | -0.216 | Destabilizing | 0.982 | D | 0.659 | prob.neutral | None | None | None | None | N |
| T/M | 0.1201 | likely_benign | 0.116 | benign | 0.03 | Stabilizing | 1.0 | D | 0.669 | prob.neutral | None | None | None | None | N |
| T/N | 0.3015 | likely_benign | 0.2785 | benign | -0.478 | Destabilizing | 0.997 | D | 0.654 | prob.neutral | N | 0.488197544 | None | None | N |
| T/P | 0.2987 | likely_benign | 0.2838 | benign | -0.336 | Destabilizing | 0.999 | D | 0.667 | prob.neutral | N | 0.4811072 | None | None | N |
| T/Q | 0.3475 | ambiguous | 0.3214 | benign | -0.672 | Destabilizing | 0.679 | D | 0.323 | neutral | None | None | None | None | N |
| T/R | 0.3897 | ambiguous | 0.3335 | benign | -0.347 | Destabilizing | 0.995 | D | 0.557 | neutral | None | None | None | None | N |
| T/S | 0.2347 | likely_benign | 0.2177 | benign | -0.747 | Destabilizing | 0.976 | D | 0.501 | neutral | N | 0.484069714 | None | None | N |
| T/V | 0.1237 | likely_benign | 0.117 | benign | -0.336 | Destabilizing | 0.991 | D | 0.621 | neutral | None | None | None | None | N |
| T/W | 0.8494 | likely_pathogenic | 0.8134 | pathogenic | -0.852 | Destabilizing | 1.0 | D | 0.707 | prob.delet. | None | None | None | None | N |
| T/Y | 0.5191 | ambiguous | 0.4688 | ambiguous | -0.609 | Destabilizing | 0.999 | D | 0.785 | 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.