Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29273 | 88042;88043;88044 | chr2:178557445;178557444;178557443 | chr2:179422172;179422171;179422170 |
| N2AB | 27632 | 83119;83120;83121 | chr2:178557445;178557444;178557443 | chr2:179422172;179422171;179422170 |
| N2A | 26705 | 80338;80339;80340 | chr2:178557445;178557444;178557443 | chr2:179422172;179422171;179422170 |
| N2B | 20208 | 60847;60848;60849 | chr2:178557445;178557444;178557443 | chr2:179422172;179422171;179422170 |
| Novex-1 | 20333 | 61222;61223;61224 | chr2:178557445;178557444;178557443 | chr2:179422172;179422171;179422170 |
| Novex-2 | 20400 | 61423;61424;61425 | chr2:178557445;178557444;178557443 | chr2:179422172;179422171;179422170 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/D | None | None | 1.0 | N | 0.728 | 0.474 | 0.459906663326 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| H/Q | None | None | 1.0 | N | 0.77 | 0.298 | 0.378674557249 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| H/R | rs1218145435  |
-1.75 | 1.0 | N | 0.748 | 0.518 | 0.414670632993 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| H/R | rs1218145435 |
-1.75 | 1.0 | N | 0.748 | 0.518 | 0.414670632993 | gnomAD-4.0.0 | 3.18205E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8578E-06 | 1.43271E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/A | 0.8965 | likely_pathogenic | 0.9097 | pathogenic | -1.822 | Destabilizing | 0.999 | D | 0.659 | neutral | None | None | None | None | N |
| H/C | 0.4084 | ambiguous | 0.4775 | ambiguous | -0.993 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | N |
| H/D | 0.9181 | likely_pathogenic | 0.9324 | pathogenic | -1.787 | Destabilizing | 1.0 | D | 0.728 | prob.delet. | N | 0.515515854 | None | None | N |
| H/E | 0.8947 | likely_pathogenic | 0.8936 | pathogenic | -1.604 | Destabilizing | 0.999 | D | 0.615 | neutral | None | None | None | None | N |
| H/F | 0.4966 | ambiguous | 0.4966 | ambiguous | 0.134 | Stabilizing | 1.0 | D | 0.77 | deleterious | None | None | None | None | N |
| H/G | 0.9411 | likely_pathogenic | 0.9509 | pathogenic | -2.216 | Highly Destabilizing | 0.999 | D | 0.689 | prob.neutral | None | None | None | None | N |
| H/I | 0.5808 | likely_pathogenic | 0.6072 | pathogenic | -0.654 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| H/K | 0.7981 | likely_pathogenic | 0.7928 | pathogenic | -1.447 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| H/L | 0.3627 | ambiguous | 0.402 | ambiguous | -0.654 | Destabilizing | 1.0 | D | 0.741 | deleterious | N | 0.474842668 | None | None | N |
| H/M | 0.8184 | likely_pathogenic | 0.8239 | pathogenic | -0.819 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | N |
| H/N | 0.4962 | ambiguous | 0.5148 | ambiguous | -1.941 | Destabilizing | 0.999 | D | 0.621 | neutral | N | 0.504664143 | None | None | N |
| H/P | 0.9806 | likely_pathogenic | 0.9867 | pathogenic | -1.035 | Destabilizing | 1.0 | D | 0.746 | deleterious | N | 0.505095306 | None | None | N |
| H/Q | 0.6291 | likely_pathogenic | 0.6503 | pathogenic | -1.505 | Destabilizing | 1.0 | D | 0.77 | deleterious | N | 0.515169138 | None | None | N |
| H/R | 0.3977 | ambiguous | 0.432 | ambiguous | -1.803 | Destabilizing | 1.0 | D | 0.748 | deleterious | N | 0.500218328 | None | None | N |
| H/S | 0.7848 | likely_pathogenic | 0.8073 | pathogenic | -2.008 | Highly Destabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | N |
| H/T | 0.7794 | likely_pathogenic | 0.8004 | pathogenic | -1.722 | Destabilizing | 1.0 | D | 0.724 | prob.delet. | None | None | None | None | N |
| H/V | 0.5856 | likely_pathogenic | 0.6281 | pathogenic | -1.035 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| H/W | 0.4978 | ambiguous | 0.5372 | ambiguous | 0.588 | Stabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | None | N |
| H/Y | 0.1808 | likely_benign | 0.1948 | benign | 0.38 | Stabilizing | 0.999 | D | 0.635 | neutral | N | 0.492679067 | 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.