Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21094 | 63505;63506;63507 | chr2:178588127;178588126;178588125 | chr2:179452854;179452853;179452852 |
| N2AB | 19453 | 58582;58583;58584 | chr2:178588127;178588126;178588125 | chr2:179452854;179452853;179452852 |
| N2A | 18526 | 55801;55802;55803 | chr2:178588127;178588126;178588125 | chr2:179452854;179452853;179452852 |
| N2B | 12029 | 36310;36311;36312 | chr2:178588127;178588126;178588125 | chr2:179452854;179452853;179452852 |
| Novex-1 | 12154 | 36685;36686;36687 | chr2:178588127;178588126;178588125 | chr2:179452854;179452853;179452852 |
| Novex-2 | 12221 | 36886;36887;36888 | chr2:178588127;178588126;178588125 | chr2:179452854;179452853;179452852 |
| 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 | rs1408476291  |
None | 0.716 | N | 0.692 | 0.184 | 0.354183961838 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| A/T | rs1408476291 |
None | 0.716 | N | 0.692 | 0.184 | 0.354183961838 | gnomAD-4.0.0 | 5.13148E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.58571E-06 | 0 | 0 |
| A/V | None | None | 0.834 | N | 0.741 | 0.277 | 0.459192005304 | gnomAD-4.0.0 | 7.5313E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.89901E-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 | 0.5826 | likely_pathogenic | 0.4389 | ambiguous | -0.747 | Destabilizing | 0.994 | D | 0.804 | deleterious | None | None | None | None | I |
| A/D | 0.8879 | likely_pathogenic | 0.8284 | pathogenic | -0.891 | Destabilizing | 0.959 | D | 0.826 | deleterious | None | None | None | None | I |
| A/E | 0.8366 | likely_pathogenic | 0.7688 | pathogenic | -1.033 | Destabilizing | 0.898 | D | 0.805 | deleterious | N | 0.465924281 | None | None | I |
| A/F | 0.6648 | likely_pathogenic | 0.5567 | ambiguous | -1.07 | Destabilizing | 0.979 | D | 0.837 | deleterious | None | None | None | None | I |
| A/G | 0.2928 | likely_benign | 0.2116 | benign | -0.667 | Destabilizing | 0.716 | D | 0.618 | neutral | N | 0.493905644 | None | None | I |
| A/H | 0.8006 | likely_pathogenic | 0.7291 | pathogenic | -0.764 | Destabilizing | 0.994 | D | 0.825 | deleterious | None | None | None | None | I |
| A/I | 0.7673 | likely_pathogenic | 0.6427 | pathogenic | -0.465 | Destabilizing | 0.959 | D | 0.817 | deleterious | None | None | None | None | I |
| A/K | 0.892 | likely_pathogenic | 0.8501 | pathogenic | -0.946 | Destabilizing | 0.921 | D | 0.813 | deleterious | None | None | None | None | I |
| A/L | 0.4055 | ambiguous | 0.3139 | benign | -0.465 | Destabilizing | 0.87 | D | 0.761 | deleterious | None | None | None | None | I |
| A/M | 0.5023 | ambiguous | 0.4008 | ambiguous | -0.341 | Destabilizing | 0.998 | D | 0.816 | deleterious | None | None | None | None | I |
| A/N | 0.7509 | likely_pathogenic | 0.6439 | pathogenic | -0.541 | Destabilizing | 0.921 | D | 0.823 | deleterious | None | None | None | None | I |
| A/P | 0.9859 | likely_pathogenic | 0.9771 | pathogenic | -0.46 | Destabilizing | 0.946 | D | 0.818 | deleterious | N | 0.486309942 | None | None | I |
| A/Q | 0.7231 | likely_pathogenic | 0.6442 | pathogenic | -0.853 | Destabilizing | 0.959 | D | 0.828 | deleterious | None | None | None | None | I |
| A/R | 0.8177 | likely_pathogenic | 0.7772 | pathogenic | -0.427 | Destabilizing | 0.959 | D | 0.819 | deleterious | None | None | None | None | I |
| A/S | 0.1256 | likely_benign | 0.0984 | benign | -0.742 | Destabilizing | 0.035 | N | 0.556 | neutral | N | 0.389109195 | None | None | I |
| A/T | 0.2805 | likely_benign | 0.2202 | benign | -0.809 | Destabilizing | 0.716 | D | 0.692 | prob.neutral | N | 0.483118221 | None | None | I |
| A/V | 0.4843 | ambiguous | 0.3758 | ambiguous | -0.46 | Destabilizing | 0.834 | D | 0.741 | deleterious | N | 0.469647264 | None | None | I |
| A/W | 0.9471 | likely_pathogenic | 0.913 | pathogenic | -1.235 | Destabilizing | 0.998 | D | 0.825 | deleterious | None | None | None | None | I |
| A/Y | 0.8035 | likely_pathogenic | 0.7136 | pathogenic | -0.895 | Destabilizing | 0.994 | D | 0.837 | deleterious | 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.