Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17375 | 52348;52349;52350 | chr2:178608888;178608887;178608886 | chr2:179473615;179473614;179473613 |
| N2AB | 15734 | 47425;47426;47427 | chr2:178608888;178608887;178608886 | chr2:179473615;179473614;179473613 |
| N2A | 14807 | 44644;44645;44646 | chr2:178608888;178608887;178608886 | chr2:179473615;179473614;179473613 |
| N2B | 8310 | 25153;25154;25155 | chr2:178608888;178608887;178608886 | chr2:179473615;179473614;179473613 |
| Novex-1 | 8435 | 25528;25529;25530 | chr2:178608888;178608887;178608886 | chr2:179473615;179473614;179473613 |
| Novex-2 | 8502 | 25729;25730;25731 | chr2:178608888;178608887;178608886 | chr2:179473615;179473614;179473613 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/Y | rs1196364304  |
-0.141 | 1.0 | N | 0.723 | 0.579 | 0.678215480895 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.66722E-04 |
| N/Y | rs1196364304 |
-0.141 | 1.0 | N | 0.723 | 0.579 | 0.678215480895 | gnomAD-4.0.0 | 3.19963E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 2.42131E-04 | 2.86313E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.4535 | ambiguous | 0.3837 | ambiguous | -0.225 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | I |
| N/C | 0.5088 | ambiguous | 0.4108 | ambiguous | 0.2 | Stabilizing | 1.0 | D | 0.72 | prob.delet. | None | None | None | None | I |
| N/D | 0.2215 | likely_benign | 0.1912 | benign | 0.218 | Stabilizing | 0.999 | D | 0.585 | neutral | N | 0.478523265 | None | None | I |
| N/E | 0.666 | likely_pathogenic | 0.6142 | pathogenic | 0.198 | Stabilizing | 0.999 | D | 0.701 | prob.neutral | None | None | None | None | I |
| N/F | 0.8551 | likely_pathogenic | 0.8042 | pathogenic | -0.55 | Destabilizing | 1.0 | D | 0.736 | prob.delet. | None | None | None | None | I |
| N/G | 0.3862 | ambiguous | 0.3234 | benign | -0.408 | Destabilizing | 0.999 | D | 0.541 | neutral | None | None | None | None | I |
| N/H | 0.1742 | likely_benign | 0.1465 | benign | -0.354 | Destabilizing | 1.0 | D | 0.641 | neutral | N | 0.473884589 | None | None | I |
| N/I | 0.7746 | likely_pathogenic | 0.7084 | pathogenic | 0.167 | Stabilizing | 1.0 | D | 0.765 | deleterious | N | 0.501521497 | None | None | I |
| N/K | 0.5802 | likely_pathogenic | 0.4963 | ambiguous | 0.059 | Stabilizing | 1.0 | D | 0.714 | prob.delet. | N | 0.497957175 | None | None | I |
| N/L | 0.6386 | likely_pathogenic | 0.5652 | pathogenic | 0.167 | Stabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | I |
| N/M | 0.7862 | likely_pathogenic | 0.7153 | pathogenic | 0.255 | Stabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | I |
| N/P | 0.8907 | likely_pathogenic | 0.8737 | pathogenic | 0.064 | Stabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | I |
| N/Q | 0.538 | ambiguous | 0.4636 | ambiguous | -0.393 | Destabilizing | 1.0 | D | 0.678 | prob.neutral | None | None | None | None | I |
| N/R | 0.5165 | ambiguous | 0.4495 | ambiguous | 0.093 | Stabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | I |
| N/S | 0.1342 | likely_benign | 0.12 | benign | -0.221 | Destabilizing | 0.999 | D | 0.538 | neutral | N | 0.498130533 | None | None | I |
| N/T | 0.3807 | ambiguous | 0.3266 | benign | -0.096 | Destabilizing | 0.999 | D | 0.697 | prob.neutral | D | 0.527933365 | None | None | I |
| N/V | 0.7201 | likely_pathogenic | 0.6486 | pathogenic | 0.064 | Stabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | I |
| N/W | 0.933 | likely_pathogenic | 0.9132 | pathogenic | -0.562 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | I |
| N/Y | 0.4101 | ambiguous | 0.3475 | ambiguous | -0.282 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | N | 0.513638271 | 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.