Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15006 | 45241;45242;45243 | chr2:178621906;178621905;178621904 | chr2:179486633;179486632;179486631 |
| N2AB | 13365 | 40318;40319;40320 | chr2:178621906;178621905;178621904 | chr2:179486633;179486632;179486631 |
| N2A | 12438 | 37537;37538;37539 | chr2:178621906;178621905;178621904 | chr2:179486633;179486632;179486631 |
| N2B | 5941 | 18046;18047;18048 | chr2:178621906;178621905;178621904 | chr2:179486633;179486632;179486631 |
| Novex-1 | 6066 | 18421;18422;18423 | chr2:178621906;178621905;178621904 | chr2:179486633;179486632;179486631 |
| Novex-2 | 6133 | 18622;18623;18624 | chr2:178621906;178621905;178621904 | chr2:179486633;179486632;179486631 |
| 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/E | rs962116921  |
None | 0.001 | N | 0.268 | 0.066 | 0.0611884634855 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 0 | 0 | 4.38597E-03 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/E | rs962116921 |
None | 0.001 | N | 0.268 | 0.066 | 0.0611884634855 | gnomAD-4.0.0 | 2.63193E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/Y | rs557941825 |
-0.074 | 0.859 | D | 0.6 | 0.274 | 0.402755899245 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 1.94477E-04 | None | 0 | 0 | 0 | 0 | 0 |
| D/Y | rs557941825 |
-0.074 | 0.859 | D | 0.6 | 0.274 | 0.402755899245 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| D/Y | rs557941825 |
-0.074 | 0.859 | D | 0.6 | 0.274 | 0.402755899245 | gnomAD-4.0.0 | 6.57488E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.94932E-04 | None | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1925 | likely_benign | 0.2073 | benign | -0.071 | Destabilizing | 0.001 | N | 0.316 | neutral | N | 0.450922572 | None | None | I |
| D/C | 0.7551 | likely_pathogenic | 0.7735 | pathogenic | -0.038 | Destabilizing | 0.909 | D | 0.641 | neutral | None | None | None | None | I |
| D/E | 0.1504 | likely_benign | 0.179 | benign | -0.188 | Destabilizing | 0.001 | N | 0.268 | neutral | N | 0.440566939 | None | None | I |
| D/F | 0.7234 | likely_pathogenic | 0.7396 | pathogenic | -0.1 | Destabilizing | 0.726 | D | 0.599 | neutral | None | None | None | None | I |
| D/G | 0.1663 | likely_benign | 0.1892 | benign | -0.209 | Destabilizing | 0.124 | N | 0.454 | neutral | N | 0.43557686 | None | None | I |
| D/H | 0.3843 | ambiguous | 0.3901 | ambiguous | 0.352 | Stabilizing | 0.788 | D | 0.433 | neutral | N | 0.499449923 | None | None | I |
| D/I | 0.5123 | ambiguous | 0.5279 | ambiguous | 0.23 | Stabilizing | 0.567 | D | 0.592 | neutral | None | None | None | None | I |
| D/K | 0.4622 | ambiguous | 0.4708 | ambiguous | 0.429 | Stabilizing | 0.157 | N | 0.41 | neutral | None | None | None | None | I |
| D/L | 0.4986 | ambiguous | 0.5274 | ambiguous | 0.23 | Stabilizing | 0.396 | N | 0.538 | neutral | None | None | None | None | I |
| D/M | 0.7106 | likely_pathogenic | 0.7338 | pathogenic | 0.15 | Stabilizing | 0.968 | D | 0.607 | neutral | None | None | None | None | I |
| D/N | 0.115 | likely_benign | 0.1226 | benign | 0.185 | Stabilizing | 0.002 | N | 0.258 | neutral | N | 0.470981188 | None | None | I |
| D/P | 0.7147 | likely_pathogenic | 0.7172 | pathogenic | 0.15 | Stabilizing | 0.726 | D | 0.42 | neutral | None | None | None | None | I |
| D/Q | 0.3993 | ambiguous | 0.4309 | ambiguous | 0.205 | Stabilizing | 0.396 | N | 0.395 | neutral | None | None | None | None | I |
| D/R | 0.5084 | ambiguous | 0.5144 | ambiguous | 0.627 | Stabilizing | 0.567 | D | 0.525 | neutral | None | None | None | None | I |
| D/S | 0.1346 | likely_benign | 0.1405 | benign | 0.08 | Stabilizing | 0.157 | N | 0.439 | neutral | None | None | None | None | I |
| D/T | 0.2759 | likely_benign | 0.2953 | benign | 0.193 | Stabilizing | 0.157 | N | 0.406 | neutral | None | None | None | None | I |
| D/V | 0.3272 | likely_benign | 0.3519 | ambiguous | 0.15 | Stabilizing | 0.331 | N | 0.535 | neutral | D | 0.588216427 | None | None | I |
| D/W | 0.8953 | likely_pathogenic | 0.89 | pathogenic | -0.028 | Destabilizing | 0.968 | D | 0.686 | prob.neutral | None | None | None | None | I |
| D/Y | 0.3488 | ambiguous | 0.3581 | ambiguous | 0.128 | Stabilizing | 0.859 | D | 0.6 | neutral | D | 0.588216427 | 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.