Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32176 | 96751;96752;96753 | chr2:178543447;178543446;178543445 | chr2:179408174;179408173;179408172 |
| N2AB | 30535 | 91828;91829;91830 | chr2:178543447;178543446;178543445 | chr2:179408174;179408173;179408172 |
| N2A | 29608 | 89047;89048;89049 | chr2:178543447;178543446;178543445 | chr2:179408174;179408173;179408172 |
| N2B | 23111 | 69556;69557;69558 | chr2:178543447;178543446;178543445 | chr2:179408174;179408173;179408172 |
| Novex-1 | 23236 | 69931;69932;69933 | chr2:178543447;178543446;178543445 | chr2:179408174;179408173;179408172 |
| Novex-2 | 23303 | 70132;70133;70134 | chr2:178543447;178543446;178543445 | chr2:179408174;179408173;179408172 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/N | rs377291343  |
-1.974 | 0.999 | N | 0.714 | 0.47 | None | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | N | None | 1.65303E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| Y/N | rs377291343 |
-1.974 | 0.999 | N | 0.714 | 0.47 | None | gnomAD-3.1.2 | 5.91E-05 | None | None | None | None | N | None | 1.92994E-04 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| Y/N | rs377291343 |
-1.974 | 0.999 | N | 0.714 | 0.47 | None | gnomAD-4.0.0 | 8.05597E-06 | None | None | None | None | N | None | 1.60171E-04 | 1.66706E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.832 | likely_pathogenic | 0.804 | pathogenic | -2.778 | Highly Destabilizing | 0.99 | D | 0.602 | neutral | None | None | None | None | N |
| Y/C | 0.2785 | likely_benign | 0.2608 | benign | -1.14 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | N | 0.515286568 | None | None | N |
| Y/D | 0.8847 | likely_pathogenic | 0.8582 | pathogenic | -2.383 | Highly Destabilizing | 0.999 | D | 0.73 | prob.delet. | N | 0.492948426 | None | None | N |
| Y/E | 0.9632 | likely_pathogenic | 0.95 | pathogenic | -2.21 | Highly Destabilizing | 0.999 | D | 0.701 | prob.neutral | None | None | None | None | N |
| Y/F | 0.1242 | likely_benign | 0.1177 | benign | -0.96 | Destabilizing | 0.006 | N | 0.249 | neutral | N | 0.42147233 | None | None | N |
| Y/G | 0.8057 | likely_pathogenic | 0.7853 | pathogenic | -3.141 | Highly Destabilizing | 0.999 | D | 0.675 | neutral | None | None | None | None | N |
| Y/H | 0.4197 | ambiguous | 0.3712 | ambiguous | -1.552 | Destabilizing | 0.996 | D | 0.632 | neutral | N | 0.499509039 | None | None | N |
| Y/I | 0.7794 | likely_pathogenic | 0.757 | pathogenic | -1.593 | Destabilizing | 0.653 | D | 0.583 | neutral | None | None | None | None | N |
| Y/K | 0.9035 | likely_pathogenic | 0.9021 | pathogenic | -1.404 | Destabilizing | 0.992 | D | 0.7 | prob.neutral | None | None | None | None | N |
| Y/L | 0.7137 | likely_pathogenic | 0.6719 | pathogenic | -1.593 | Destabilizing | 0.28 | N | 0.604 | neutral | None | None | None | None | N |
| Y/M | 0.8529 | likely_pathogenic | 0.835 | pathogenic | -1.268 | Destabilizing | 0.997 | D | 0.67 | neutral | None | None | None | None | N |
| Y/N | 0.6277 | likely_pathogenic | 0.5724 | pathogenic | -1.937 | Destabilizing | 0.999 | D | 0.714 | prob.delet. | N | 0.491214843 | None | None | N |
| Y/P | 0.9915 | likely_pathogenic | 0.9921 | pathogenic | -1.997 | Destabilizing | 0.999 | D | 0.753 | deleterious | None | None | None | None | N |
| Y/Q | 0.8532 | likely_pathogenic | 0.8243 | pathogenic | -1.813 | Destabilizing | 0.997 | D | 0.669 | neutral | None | None | None | None | N |
| Y/R | 0.7502 | likely_pathogenic | 0.7373 | pathogenic | -1.072 | Destabilizing | 0.998 | D | 0.716 | prob.delet. | None | None | None | None | N |
| Y/S | 0.5319 | ambiguous | 0.4831 | ambiguous | -2.404 | Highly Destabilizing | 0.999 | D | 0.651 | neutral | N | 0.44982958 | None | None | N |
| Y/T | 0.7662 | likely_pathogenic | 0.7401 | pathogenic | -2.131 | Highly Destabilizing | 0.999 | D | 0.651 | neutral | None | None | None | None | N |
| Y/V | 0.6709 | likely_pathogenic | 0.6526 | pathogenic | -1.997 | Destabilizing | 0.98 | D | 0.564 | neutral | None | None | None | None | N |
| Y/W | 0.5696 | likely_pathogenic | 0.5798 | pathogenic | -0.234 | Destabilizing | 0.998 | D | 0.633 | 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.