Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15455 | 46588;46589;46590 | chr2:178620054;178620053;178620052 | chr2:179484781;179484780;179484779 |
| N2AB | 13814 | 41665;41666;41667 | chr2:178620054;178620053;178620052 | chr2:179484781;179484780;179484779 |
| N2A | 12887 | 38884;38885;38886 | chr2:178620054;178620053;178620052 | chr2:179484781;179484780;179484779 |
| N2B | 6390 | 19393;19394;19395 | chr2:178620054;178620053;178620052 | chr2:179484781;179484780;179484779 |
| Novex-1 | 6515 | 19768;19769;19770 | chr2:178620054;178620053;178620052 | chr2:179484781;179484780;179484779 |
| Novex-2 | 6582 | 19969;19970;19971 | chr2:178620054;178620053;178620052 | chr2:179484781;179484780;179484779 |
| 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/N | rs370813526  |
0.112 | 0.83 | D | 0.65 | 0.481 | None | gnomAD-2.1.1 | 5.67E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.65E-05 | 1.16655E-04 | 0 |
| D/N | rs370813526 |
0.112 | 0.83 | D | 0.65 | 0.481 | None | gnomAD-3.1.2 | 4.61E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.03108E-04 | 0 | 0 |
| D/N | rs370813526 |
0.112 | 0.83 | D | 0.65 | 0.481 | None | gnomAD-4.0.0 | 9.11989E-05 | None | None | None | None | N | None | 0 | 3.34303E-05 | None | 0 | 0 | None | 1.25063E-04 | 1.64853E-04 | 1.12825E-04 | 0 | 4.81108E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.3188 | likely_benign | 0.3634 | ambiguous | -0.233 | Destabilizing | 0.41 | N | 0.625 | neutral | D | 0.544211185 | None | None | N |
| D/C | 0.883 | likely_pathogenic | 0.9088 | pathogenic | 0.047 | Stabilizing | 0.993 | D | 0.749 | deleterious | None | None | None | None | N |
| D/E | 0.1343 | likely_benign | 0.2051 | benign | -0.245 | Destabilizing | 0.004 | N | 0.263 | neutral | N | 0.489468376 | None | None | N |
| D/F | 0.8252 | likely_pathogenic | 0.8632 | pathogenic | -0.304 | Destabilizing | 0.993 | D | 0.75 | deleterious | None | None | None | None | N |
| D/G | 0.3324 | likely_benign | 0.375 | ambiguous | -0.393 | Destabilizing | 0.581 | D | 0.639 | neutral | D | 0.543482743 | None | None | N |
| D/H | 0.6239 | likely_pathogenic | 0.6768 | pathogenic | -0.057 | Destabilizing | 0.974 | D | 0.716 | prob.delet. | D | 0.543122302 | None | None | N |
| D/I | 0.6193 | likely_pathogenic | 0.6906 | pathogenic | 0.131 | Stabilizing | 0.929 | D | 0.767 | deleterious | None | None | None | None | N |
| D/K | 0.63 | likely_pathogenic | 0.6988 | pathogenic | 0.296 | Stabilizing | 0.764 | D | 0.684 | prob.neutral | None | None | None | None | N |
| D/L | 0.6111 | likely_pathogenic | 0.6895 | pathogenic | 0.131 | Stabilizing | 0.866 | D | 0.75 | deleterious | None | None | None | None | N |
| D/M | 0.7909 | likely_pathogenic | 0.8546 | pathogenic | 0.232 | Stabilizing | 0.993 | D | 0.741 | deleterious | None | None | None | None | N |
| D/N | 0.2267 | likely_benign | 0.2669 | benign | 0.13 | Stabilizing | 0.83 | D | 0.65 | neutral | D | 0.595463845 | None | None | N |
| D/P | 0.8168 | likely_pathogenic | 0.8485 | pathogenic | 0.03 | Stabilizing | 0.929 | D | 0.723 | prob.delet. | None | None | None | None | N |
| D/Q | 0.5221 | ambiguous | 0.6111 | pathogenic | 0.139 | Stabilizing | 0.764 | D | 0.705 | prob.neutral | None | None | None | None | N |
| D/R | 0.6915 | likely_pathogenic | 0.7391 | pathogenic | 0.45 | Stabilizing | 0.764 | D | 0.73 | prob.delet. | None | None | None | None | N |
| D/S | 0.2492 | likely_benign | 0.2815 | benign | 0.003 | Stabilizing | 0.48 | N | 0.576 | neutral | None | None | None | None | N |
| D/T | 0.4203 | ambiguous | 0.4898 | ambiguous | 0.123 | Stabilizing | 0.866 | D | 0.69 | prob.neutral | None | None | None | None | N |
| D/V | 0.4468 | ambiguous | 0.5019 | ambiguous | 0.03 | Stabilizing | 0.83 | D | 0.75 | deleterious | D | 0.617989477 | None | None | N |
| D/W | 0.9354 | likely_pathogenic | 0.9502 | pathogenic | -0.222 | Destabilizing | 0.993 | D | 0.755 | deleterious | None | None | None | None | N |
| D/Y | 0.5645 | likely_pathogenic | 0.6023 | pathogenic | -0.083 | Destabilizing | 0.991 | D | 0.749 | deleterious | D | 0.634599555 | 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.