Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20549 | 61870;61871;61872 | chr2:178590080;178590079;178590078 | chr2:179454807;179454806;179454805 |
| N2AB | 18908 | 56947;56948;56949 | chr2:178590080;178590079;178590078 | chr2:179454807;179454806;179454805 |
| N2A | 17981 | 54166;54167;54168 | chr2:178590080;178590079;178590078 | chr2:179454807;179454806;179454805 |
| N2B | 11484 | 34675;34676;34677 | chr2:178590080;178590079;178590078 | chr2:179454807;179454806;179454805 |
| Novex-1 | 11609 | 35050;35051;35052 | chr2:178590080;178590079;178590078 | chr2:179454807;179454806;179454805 |
| Novex-2 | 11676 | 35251;35252;35253 | chr2:178590080;178590079;178590078 | chr2:179454807;179454806;179454805 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/F | rs750680415  |
None | 0.989 | N | 0.749 | 0.298 | 0.523133305157 | gnomAD-4.0.0 | 1.36896E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79946E-06 | 0 | 0 |
| I/M | None | None | 0.989 | N | 0.705 | 0.288 | 0.470072546239 | gnomAD-4.0.0 | 6.8445E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99683E-07 | 0 | 0 |
| I/T | None | None | 0.98 | N | 0.717 | 0.408 | 0.611003947198 | gnomAD-4.0.0 | 1.36889E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99674E-07 | 0 | 1.65717E-05 |
| I/V | rs750680415 |
-1.333 | 0.689 | N | 0.399 | 0.117 | 0.371903410333 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | N | None | 1.29216E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs750680415 |
-1.333 | 0.689 | N | 0.399 | 0.117 | 0.371903410333 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.82E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs750680415 |
-1.333 | 0.689 | N | 0.399 | 0.117 | 0.371903410333 | gnomAD-4.0.0 | 1.85984E-06 | None | None | None | None | N | None | 4.00588E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9621 | likely_pathogenic | 0.9665 | pathogenic | -2.137 | Highly Destabilizing | 0.965 | D | 0.707 | prob.neutral | None | None | None | None | N |
| I/C | 0.9601 | likely_pathogenic | 0.9579 | pathogenic | -1.672 | Destabilizing | 1.0 | D | 0.778 | deleterious | None | None | None | None | N |
| I/D | 0.9997 | likely_pathogenic | 0.9998 | pathogenic | -1.622 | Destabilizing | 0.999 | D | 0.842 | deleterious | None | None | None | None | N |
| I/E | 0.9992 | likely_pathogenic | 0.9994 | pathogenic | -1.423 | Destabilizing | 0.999 | D | 0.836 | deleterious | None | None | None | None | N |
| I/F | 0.7088 | likely_pathogenic | 0.7361 | pathogenic | -1.323 | Destabilizing | 0.989 | D | 0.749 | deleterious | N | 0.509426883 | None | None | N |
| I/G | 0.9962 | likely_pathogenic | 0.997 | pathogenic | -2.662 | Highly Destabilizing | 0.999 | D | 0.825 | deleterious | None | None | None | None | N |
| I/H | 0.998 | likely_pathogenic | 0.9985 | pathogenic | -2.03 | Highly Destabilizing | 1.0 | D | 0.852 | deleterious | None | None | None | None | N |
| I/K | 0.9976 | likely_pathogenic | 0.9983 | pathogenic | -1.325 | Destabilizing | 0.999 | D | 0.824 | deleterious | None | None | None | None | N |
| I/L | 0.2158 | likely_benign | 0.218 | benign | -0.651 | Destabilizing | 0.011 | N | 0.359 | neutral | N | 0.387020534 | None | None | N |
| I/M | 0.4831 | ambiguous | 0.4987 | ambiguous | -0.754 | Destabilizing | 0.989 | D | 0.705 | prob.neutral | N | 0.496113656 | None | None | N |
| I/N | 0.9953 | likely_pathogenic | 0.9967 | pathogenic | -1.546 | Destabilizing | 0.998 | D | 0.845 | deleterious | N | 0.467670757 | None | None | N |
| I/P | 0.9974 | likely_pathogenic | 0.9978 | pathogenic | -1.123 | Destabilizing | 0.999 | D | 0.843 | deleterious | None | None | None | None | N |
| I/Q | 0.9973 | likely_pathogenic | 0.9979 | pathogenic | -1.422 | Destabilizing | 0.999 | D | 0.84 | deleterious | None | None | None | None | N |
| I/R | 0.995 | likely_pathogenic | 0.9962 | pathogenic | -1.146 | Destabilizing | 0.999 | D | 0.843 | deleterious | None | None | None | None | N |
| I/S | 0.9902 | likely_pathogenic | 0.9925 | pathogenic | -2.383 | Highly Destabilizing | 0.998 | D | 0.767 | deleterious | N | 0.467417268 | None | None | N |
| I/T | 0.9743 | likely_pathogenic | 0.9814 | pathogenic | -2.02 | Highly Destabilizing | 0.98 | D | 0.717 | prob.delet. | N | 0.467163778 | None | None | N |
| I/V | 0.1429 | likely_benign | 0.1518 | benign | -1.123 | Destabilizing | 0.689 | D | 0.399 | neutral | N | 0.430309952 | None | None | N |
| I/W | 0.9973 | likely_pathogenic | 0.9976 | pathogenic | -1.541 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| I/Y | 0.9825 | likely_pathogenic | 0.9863 | pathogenic | -1.241 | Destabilizing | 0.999 | D | 0.772 | 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.