Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 34282 | 103069;103070;103071 | chr2:178533771;178533770;178533769 | chr2:179398498;179398497;179398496 |
| N2AB | 32641 | 98146;98147;98148 | chr2:178533771;178533770;178533769 | chr2:179398498;179398497;179398496 |
| N2A | 31714 | 95365;95366;95367 | chr2:178533771;178533770;178533769 | chr2:179398498;179398497;179398496 |
| N2B | 25217 | 75874;75875;75876 | chr2:178533771;178533770;178533769 | chr2:179398498;179398497;179398496 |
| Novex-1 | 25342 | 76249;76250;76251 | chr2:178533771;178533770;178533769 | chr2:179398498;179398497;179398496 |
| Novex-2 | 25409 | 76450;76451;76452 | chr2:178533771;178533770;178533769 | chr2:179398498;179398497;179398496 |
| 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/N | rs369595031  |
-0.65 | 0.991 | D | 0.542 | 0.428 | None | gnomAD-2.1.1 | 4.01E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/N | rs369595031 |
-0.65 | 0.991 | D | 0.542 | 0.428 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/N | rs369595031 |
-0.65 | 0.991 | D | 0.542 | 0.428 | None | gnomAD-4.0.0 | 6.56961E-06 | None | None | None | None | N | None | 2.41196E-05 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.3511 | ambiguous | 0.4065 | ambiguous | -0.391 | Destabilizing | 0.046 | N | 0.217 | neutral | N | 0.514684427 | None | None | N |
| T/C | 0.8465 | likely_pathogenic | 0.9034 | pathogenic | -0.289 | Destabilizing | 0.999 | D | 0.609 | neutral | None | None | None | None | N |
| T/D | 0.9172 | likely_pathogenic | 0.9183 | pathogenic | 0.236 | Stabilizing | 0.993 | D | 0.614 | neutral | None | None | None | None | N |
| T/E | 0.8926 | likely_pathogenic | 0.8888 | pathogenic | 0.17 | Stabilizing | 0.986 | D | 0.569 | neutral | None | None | None | None | N |
| T/F | 0.8166 | likely_pathogenic | 0.85 | pathogenic | -0.826 | Destabilizing | 0.993 | D | 0.669 | neutral | None | None | None | None | N |
| T/G | 0.7557 | likely_pathogenic | 0.8018 | pathogenic | -0.539 | Destabilizing | 0.91 | D | 0.529 | neutral | None | None | None | None | N |
| T/H | 0.8183 | likely_pathogenic | 0.824 | pathogenic | -0.837 | Destabilizing | 0.999 | D | 0.65 | neutral | None | None | None | None | N |
| T/I | 0.6849 | likely_pathogenic | 0.7064 | pathogenic | -0.12 | Destabilizing | 0.885 | D | 0.536 | neutral | D | 0.530557957 | None | None | N |
| T/K | 0.7688 | likely_pathogenic | 0.7523 | pathogenic | -0.356 | Destabilizing | 0.986 | D | 0.577 | neutral | None | None | None | None | N |
| T/L | 0.4035 | ambiguous | 0.4752 | ambiguous | -0.12 | Destabilizing | 0.91 | D | 0.433 | neutral | None | None | None | None | N |
| T/M | 0.2655 | likely_benign | 0.3273 | benign | 0.021 | Stabilizing | 0.998 | D | 0.614 | neutral | None | None | None | None | N |
| T/N | 0.6197 | likely_pathogenic | 0.6256 | pathogenic | -0.14 | Destabilizing | 0.991 | D | 0.542 | neutral | D | 0.522015831 | None | None | N |
| T/P | 0.6799 | likely_pathogenic | 0.6884 | pathogenic | -0.181 | Destabilizing | 0.991 | D | 0.628 | neutral | N | 0.506015992 | None | None | N |
| T/Q | 0.7836 | likely_pathogenic | 0.7856 | pathogenic | -0.361 | Destabilizing | 0.993 | D | 0.624 | neutral | None | None | None | None | N |
| T/R | 0.7006 | likely_pathogenic | 0.7088 | pathogenic | -0.105 | Destabilizing | 0.993 | D | 0.631 | neutral | None | None | None | None | N |
| T/S | 0.4309 | ambiguous | 0.4817 | ambiguous | -0.376 | Destabilizing | 0.885 | D | 0.412 | neutral | N | 0.463100814 | None | None | N |
| T/V | 0.5232 | ambiguous | 0.5549 | ambiguous | -0.181 | Destabilizing | 0.06 | N | 0.273 | neutral | None | None | None | None | N |
| T/W | 0.9416 | likely_pathogenic | 0.9546 | pathogenic | -0.813 | Destabilizing | 0.999 | D | 0.671 | neutral | None | None | None | None | N |
| T/Y | 0.8749 | likely_pathogenic | 0.8888 | pathogenic | -0.531 | Destabilizing | 0.998 | D | 0.667 | 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.