Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22892 | 68899;68900;68901 | chr2:178577752;178577751;178577750 | chr2:179442479;179442478;179442477 |
| N2AB | 21251 | 63976;63977;63978 | chr2:178577752;178577751;178577750 | chr2:179442479;179442478;179442477 |
| N2A | 20324 | 61195;61196;61197 | chr2:178577752;178577751;178577750 | chr2:179442479;179442478;179442477 |
| N2B | 13827 | 41704;41705;41706 | chr2:178577752;178577751;178577750 | chr2:179442479;179442478;179442477 |
| Novex-1 | 13952 | 42079;42080;42081 | chr2:178577752;178577751;178577750 | chr2:179442479;179442478;179442477 |
| Novex-2 | 14019 | 42280;42281;42282 | chr2:178577752;178577751;178577750 | chr2:179442479;179442478;179442477 |
| 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/H | None | None | 0.994 | N | 0.74 | 0.461 | 0.338834610459 | gnomAD-4.0.0 | 1.5921E-06 | None | None | None | None | N | None | 0 | 0 | None | 4.77008E-05 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| N/K | None | None | 0.067 | N | 0.441 | 0.15 | 0.143124449307 | gnomAD-4.0.0 | 6.84379E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99611E-07 | 0 | 0 |
| N/S | rs1575837418  |
None | 0.958 | N | 0.585 | 0.346 | 0.254244900254 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 3.16456E-03 | 0 | 0 | 0 |
| N/S | rs1575837418 |
None | 0.958 | N | 0.585 | 0.346 | 0.254244900254 | gnomAD-4.0.0 | 2.56304E-06 | None | None | None | None | N | None | 1.68811E-05 | 0 | None | 0 | 0 | None | 0 | 2.2553E-04 | 0 | 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 | 0.8285 | likely_pathogenic | 0.7897 | pathogenic | -0.896 | Destabilizing | 0.938 | D | 0.658 | neutral | None | None | None | None | N |
| N/C | 0.6569 | likely_pathogenic | 0.6245 | pathogenic | -0.028 | Destabilizing | 1.0 | D | 0.788 | deleterious | None | None | None | None | N |
| N/D | 0.8081 | likely_pathogenic | 0.8197 | pathogenic | -0.839 | Destabilizing | 0.958 | D | 0.635 | neutral | N | 0.481030023 | None | None | N |
| N/E | 0.9844 | likely_pathogenic | 0.9817 | pathogenic | -0.653 | Destabilizing | 0.938 | D | 0.646 | neutral | None | None | None | None | N |
| N/F | 0.9897 | likely_pathogenic | 0.9863 | pathogenic | -0.447 | Destabilizing | 1.0 | D | 0.798 | deleterious | None | None | None | None | N |
| N/G | 0.7624 | likely_pathogenic | 0.7197 | pathogenic | -1.311 | Destabilizing | 0.968 | D | 0.592 | neutral | None | None | None | None | N |
| N/H | 0.7225 | likely_pathogenic | 0.6669 | pathogenic | -0.939 | Destabilizing | 0.994 | D | 0.74 | deleterious | N | 0.484561969 | None | None | N |
| N/I | 0.9177 | likely_pathogenic | 0.8976 | pathogenic | 0.197 | Stabilizing | 0.994 | D | 0.796 | deleterious | N | 0.500602309 | None | None | N |
| N/K | 0.9892 | likely_pathogenic | 0.9849 | pathogenic | -0.233 | Destabilizing | 0.067 | N | 0.441 | neutral | N | 0.486964598 | None | None | N |
| N/L | 0.9025 | likely_pathogenic | 0.8837 | pathogenic | 0.197 | Stabilizing | 0.991 | D | 0.743 | deleterious | None | None | None | None | N |
| N/M | 0.9379 | likely_pathogenic | 0.928 | pathogenic | 0.524 | Stabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| N/P | 0.9582 | likely_pathogenic | 0.9479 | pathogenic | -0.137 | Destabilizing | 0.995 | D | 0.757 | deleterious | None | None | None | None | N |
| N/Q | 0.9614 | likely_pathogenic | 0.9522 | pathogenic | -0.758 | Destabilizing | 0.991 | D | 0.731 | prob.delet. | None | None | None | None | N |
| N/R | 0.9818 | likely_pathogenic | 0.9759 | pathogenic | -0.47 | Destabilizing | 0.982 | D | 0.702 | prob.neutral | None | None | None | None | N |
| N/S | 0.1128 | likely_benign | 0.1007 | benign | -1.072 | Destabilizing | 0.958 | D | 0.585 | neutral | N | 0.485542451 | None | None | N |
| N/T | 0.3907 | ambiguous | 0.4272 | ambiguous | -0.673 | Destabilizing | 0.958 | D | 0.653 | neutral | N | 0.472938947 | None | None | N |
| N/V | 0.8546 | likely_pathogenic | 0.8309 | pathogenic | -0.137 | Destabilizing | 0.991 | D | 0.777 | deleterious | None | None | None | None | N |
| N/W | 0.9963 | likely_pathogenic | 0.995 | pathogenic | -0.26 | Destabilizing | 1.0 | D | 0.776 | deleterious | None | None | None | None | N |
| N/Y | 0.9308 | likely_pathogenic | 0.9048 | pathogenic | 0.007 | Stabilizing | 0.998 | D | 0.779 | deleterious | N | 0.483525238 | 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.