Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24016 | 72271;72272;72273 | chr2:178574086;178574085;178574084 | chr2:179438813;179438812;179438811 |
| N2AB | 22375 | 67348;67349;67350 | chr2:178574086;178574085;178574084 | chr2:179438813;179438812;179438811 |
| N2A | 21448 | 64567;64568;64569 | chr2:178574086;178574085;178574084 | chr2:179438813;179438812;179438811 |
| N2B | 14951 | 45076;45077;45078 | chr2:178574086;178574085;178574084 | chr2:179438813;179438812;179438811 |
| Novex-1 | 15076 | 45451;45452;45453 | chr2:178574086;178574085;178574084 | chr2:179438813;179438812;179438811 |
| Novex-2 | 15143 | 45652;45653;45654 | chr2:178574086;178574085;178574084 | chr2:179438813;179438812;179438811 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/V | rs1709212928  |
None | 0.966 | N | 0.673 | 0.182 | 0.414539908741 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/V | rs1709212928 |
None | 0.966 | N | 0.673 | 0.182 | 0.414539908741 | gnomAD-4.0.0 | 2.47932E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.39109E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1212 | likely_benign | 0.1206 | benign | -0.252 | Destabilizing | 0.666 | D | 0.682 | prob.neutral | N | 0.472732577 | None | None | N |
| D/C | 0.601 | likely_pathogenic | 0.6184 | pathogenic | -0.047 | Destabilizing | 0.998 | D | 0.789 | deleterious | None | None | None | None | N |
| D/E | 0.1208 | likely_benign | 0.1189 | benign | -0.276 | Destabilizing | 0.022 | N | 0.147 | neutral | N | 0.400467047 | None | None | N |
| D/F | 0.5534 | ambiguous | 0.5691 | pathogenic | -0.166 | Destabilizing | 0.991 | D | 0.749 | deleterious | None | None | None | None | N |
| D/G | 0.1332 | likely_benign | 0.1417 | benign | -0.434 | Destabilizing | 0.012 | N | 0.45 | neutral | N | 0.426192211 | None | None | N |
| D/H | 0.2743 | likely_benign | 0.2766 | benign | 0.121 | Stabilizing | 0.997 | D | 0.656 | prob.neutral | N | 0.465728065 | None | None | N |
| D/I | 0.2964 | likely_benign | 0.2951 | benign | 0.178 | Stabilizing | 0.991 | D | 0.763 | deleterious | None | None | None | None | N |
| D/K | 0.2844 | likely_benign | 0.2787 | benign | 0.313 | Stabilizing | 0.841 | D | 0.685 | prob.delet. | None | None | None | None | N |
| D/L | 0.3136 | likely_benign | 0.3091 | benign | 0.178 | Stabilizing | 0.974 | D | 0.736 | deleterious | None | None | None | None | N |
| D/M | 0.5309 | ambiguous | 0.5345 | ambiguous | 0.226 | Stabilizing | 0.998 | D | 0.753 | deleterious | None | None | None | None | N |
| D/N | 0.1079 | likely_benign | 0.109 | benign | -0.002 | Destabilizing | 0.799 | D | 0.62 | neutral | N | 0.480351983 | None | None | N |
| D/P | 0.4019 | ambiguous | 0.3837 | ambiguous | 0.057 | Stabilizing | 0.991 | D | 0.665 | prob.neutral | None | None | None | None | N |
| D/Q | 0.2934 | likely_benign | 0.2817 | benign | 0.03 | Stabilizing | 0.949 | D | 0.573 | neutral | None | None | None | None | N |
| D/R | 0.3569 | ambiguous | 0.3572 | ambiguous | 0.526 | Stabilizing | 0.949 | D | 0.759 | deleterious | None | None | None | None | N |
| D/S | 0.1137 | likely_benign | 0.1128 | benign | -0.108 | Destabilizing | 0.841 | D | 0.571 | neutral | None | None | None | None | N |
| D/T | 0.2098 | likely_benign | 0.2058 | benign | 0.038 | Stabilizing | 0.915 | D | 0.685 | prob.delet. | None | None | None | None | N |
| D/V | 0.1655 | likely_benign | 0.1622 | benign | 0.057 | Stabilizing | 0.966 | D | 0.673 | prob.neutral | N | 0.499687105 | None | None | N |
| D/W | 0.8604 | likely_pathogenic | 0.8765 | pathogenic | -0.033 | Destabilizing | 0.998 | D | 0.79 | deleterious | None | None | None | None | N |
| D/Y | 0.2334 | likely_benign | 0.2384 | benign | 0.072 | Stabilizing | 0.989 | D | 0.747 | deleterious | N | 0.465221086 | 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.