Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29184 | 87775;87776;87777 | chr2:178557804;178557803;178557802 | chr2:179422531;179422530;179422529 |
| N2AB | 27543 | 82852;82853;82854 | chr2:178557804;178557803;178557802 | chr2:179422531;179422530;179422529 |
| N2A | 26616 | 80071;80072;80073 | chr2:178557804;178557803;178557802 | chr2:179422531;179422530;179422529 |
| N2B | 20119 | 60580;60581;60582 | chr2:178557804;178557803;178557802 | chr2:179422531;179422530;179422529 |
| Novex-1 | 20244 | 60955;60956;60957 | chr2:178557804;178557803;178557802 | chr2:179422531;179422530;179422529 |
| Novex-2 | 20311 | 61156;61157;61158 | chr2:178557804;178557803;178557802 | chr2:179422531;179422530;179422529 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | None | None | None | N | 0.091 | 0.082 | 0.0884992946249 | gnomAD-4.0.0 | 6.84167E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99429E-07 | 0 | 0 |
| V/G | None | None | 0.042 | N | 0.337 | 0.14 | 0.176091768786 | gnomAD-4.0.0 | 1.36833E-06 | None | None | None | None | I | None | 5.97372E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/L | None | None | 0.042 | N | 0.221 | 0.132 | 0.231231049324 | gnomAD-4.0.0 | 6.84161E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65645E-05 |
| V/M | rs910283551  |
-0.439 | 0.602 | N | 0.243 | 0.14 | None | gnomAD-2.1.1 | 1.2E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.66E-05 | 0 |
| V/M | rs910283551 |
-0.439 | 0.602 | N | 0.243 | 0.14 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| V/M | rs910283551 |
-0.439 | 0.602 | N | 0.243 | 0.14 | None | gnomAD-4.0.0 | 1.17731E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.5256E-05 | 0 | 1.60092E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.0737 | likely_benign | 0.1075 | benign | -0.505 | Destabilizing | None | N | 0.091 | neutral | N | 0.428243587 | None | None | I |
| V/C | 0.4986 | ambiguous | 0.5767 | pathogenic | -0.568 | Destabilizing | 0.667 | D | 0.249 | neutral | None | None | None | None | I |
| V/D | 0.1893 | likely_benign | 0.265 | benign | -0.289 | Destabilizing | 0.055 | N | 0.315 | neutral | None | None | None | None | I |
| V/E | 0.1899 | likely_benign | 0.2535 | benign | -0.397 | Destabilizing | 0.081 | N | 0.299 | neutral | N | 0.415388932 | None | None | I |
| V/F | 0.1271 | likely_benign | 0.1418 | benign | -0.707 | Destabilizing | 0.667 | D | 0.29 | neutral | None | None | None | None | I |
| V/G | 0.1034 | likely_benign | 0.1416 | benign | -0.643 | Destabilizing | 0.042 | N | 0.337 | neutral | N | 0.453504603 | None | None | I |
| V/H | 0.3592 | ambiguous | 0.4344 | ambiguous | -0.185 | Destabilizing | 0.667 | D | 0.301 | neutral | None | None | None | None | I |
| V/I | 0.0733 | likely_benign | 0.0739 | benign | -0.288 | Destabilizing | 0.104 | N | 0.293 | neutral | None | None | None | None | I |
| V/K | 0.248 | likely_benign | 0.3191 | benign | -0.438 | Destabilizing | 0.104 | N | 0.303 | neutral | None | None | None | None | I |
| V/L | 0.1061 | likely_benign | 0.1258 | benign | -0.288 | Destabilizing | 0.042 | N | 0.221 | neutral | N | 0.484712945 | None | None | I |
| V/M | 0.0958 | likely_benign | 0.1097 | benign | -0.376 | Destabilizing | 0.602 | D | 0.243 | neutral | N | 0.506397726 | None | None | I |
| V/N | 0.1021 | likely_benign | 0.1321 | benign | -0.146 | Destabilizing | 0.001 | N | 0.19 | neutral | None | None | None | None | I |
| V/P | 0.5083 | ambiguous | 0.6961 | pathogenic | -0.326 | Destabilizing | 0.364 | N | 0.321 | neutral | None | None | None | None | I |
| V/Q | 0.1951 | likely_benign | 0.2434 | benign | -0.387 | Destabilizing | 0.364 | N | 0.365 | neutral | None | None | None | None | I |
| V/R | 0.236 | likely_benign | 0.293 | benign | 0.081 | Stabilizing | 0.22 | N | 0.349 | neutral | None | None | None | None | I |
| V/S | 0.0822 | likely_benign | 0.1148 | benign | -0.508 | Destabilizing | 0.055 | N | 0.289 | neutral | None | None | None | None | I |
| V/T | 0.0877 | likely_benign | 0.1193 | benign | -0.516 | Destabilizing | 0.055 | N | 0.242 | neutral | None | None | None | None | I |
| V/W | 0.6782 | likely_pathogenic | 0.7425 | pathogenic | -0.787 | Destabilizing | 0.958 | D | 0.305 | neutral | None | None | None | None | I |
| V/Y | 0.3591 | ambiguous | 0.4243 | ambiguous | -0.489 | Destabilizing | 0.859 | D | 0.283 | neutral | None | None | None | None | I |
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.