Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28025 | 84298;84299;84300 | chr2:178562059;178562058;178562057 | chr2:179426786;179426785;179426784 |
| N2AB | 26384 | 79375;79376;79377 | chr2:178562059;178562058;178562057 | chr2:179426786;179426785;179426784 |
| N2A | 25457 | 76594;76595;76596 | chr2:178562059;178562058;178562057 | chr2:179426786;179426785;179426784 |
| N2B | 18960 | 57103;57104;57105 | chr2:178562059;178562058;178562057 | chr2:179426786;179426785;179426784 |
| Novex-1 | 19085 | 57478;57479;57480 | chr2:178562059;178562058;178562057 | chr2:179426786;179426785;179426784 |
| Novex-2 | 19152 | 57679;57680;57681 | chr2:178562059;178562058;178562057 | chr2:179426786;179426785;179426784 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/T | rs372956981  |
-1.998 | 1.0 | D | 0.681 | 0.409 | None | gnomAD-2.1.1 | 1.62E-05 | None | None | None | None | N | None | 1.2987E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.79E-05 | 0 |
| A/T | rs372956981 |
-1.998 | 1.0 | D | 0.681 | 0.409 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| A/T | rs372956981 |
-1.998 | 1.0 | D | 0.681 | 0.409 | None | gnomAD-4.0.0 | 9.29798E-06 | None | None | None | None | N | None | 4.00491E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 9.32483E-06 | 1.09835E-05 | 0 |
| A/V | None | None | 1.0 | N | 0.625 | 0.403 | 0.550632123912 | gnomAD-4.0.0 | 1.59237E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85945E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.6155 | likely_pathogenic | 0.5984 | pathogenic | -1.635 | Destabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | None | N |
| A/D | 0.9558 | likely_pathogenic | 0.966 | pathogenic | -2.603 | Highly Destabilizing | 1.0 | D | 0.832 | deleterious | D | 0.546382466 | None | None | N |
| A/E | 0.9487 | likely_pathogenic | 0.9578 | pathogenic | -2.58 | Highly Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | N |
| A/F | 0.8847 | likely_pathogenic | 0.8946 | pathogenic | -1.248 | Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | N |
| A/G | 0.2967 | likely_benign | 0.2843 | benign | -1.514 | Destabilizing | 1.0 | D | 0.559 | neutral | D | 0.534772671 | None | None | N |
| A/H | 0.9757 | likely_pathogenic | 0.9795 | pathogenic | -1.482 | Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | N |
| A/I | 0.4646 | ambiguous | 0.4238 | ambiguous | -0.572 | Destabilizing | 1.0 | D | 0.832 | deleterious | None | None | None | None | N |
| A/K | 0.9864 | likely_pathogenic | 0.9876 | pathogenic | -1.484 | Destabilizing | 1.0 | D | 0.808 | deleterious | None | None | None | None | N |
| A/L | 0.5228 | ambiguous | 0.5057 | ambiguous | -0.572 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | N |
| A/M | 0.6288 | likely_pathogenic | 0.6032 | pathogenic | -0.659 | Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | N |
| A/N | 0.8758 | likely_pathogenic | 0.8847 | pathogenic | -1.545 | Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | N |
| A/P | 0.7092 | likely_pathogenic | 0.7372 | pathogenic | -0.755 | Destabilizing | 1.0 | D | 0.831 | deleterious | D | 0.523669855 | None | None | N |
| A/Q | 0.9502 | likely_pathogenic | 0.9562 | pathogenic | -1.719 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| A/R | 0.973 | likely_pathogenic | 0.9774 | pathogenic | -1.106 | Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| A/S | 0.1731 | likely_benign | 0.1722 | benign | -1.838 | Destabilizing | 1.0 | D | 0.582 | neutral | D | 0.535102559 | None | None | N |
| A/T | 0.1553 | likely_benign | 0.1402 | benign | -1.731 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | D | 0.534294482 | None | None | N |
| A/V | 0.1959 | likely_benign | 0.1824 | benign | -0.755 | Destabilizing | 1.0 | D | 0.625 | neutral | N | 0.514334924 | None | None | N |
| A/W | 0.9894 | likely_pathogenic | 0.9908 | pathogenic | -1.633 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | N |
| A/Y | 0.9552 | likely_pathogenic | 0.9614 | pathogenic | -1.232 | Destabilizing | 1.0 | D | 0.847 | 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.