Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 34145 | 102658;102659;102660 | chr2:178534182;178534181;178534180 | chr2:179398909;179398908;179398907 |
| N2AB | 32504 | 97735;97736;97737 | chr2:178534182;178534181;178534180 | chr2:179398909;179398908;179398907 |
| N2A | 31577 | 94954;94955;94956 | chr2:178534182;178534181;178534180 | chr2:179398909;179398908;179398907 |
| N2B | 25080 | 75463;75464;75465 | chr2:178534182;178534181;178534180 | chr2:179398909;179398908;179398907 |
| Novex-1 | 25205 | 75838;75839;75840 | chr2:178534182;178534181;178534180 | chr2:179398909;179398908;179398907 |
| Novex-2 | 25272 | 76039;76040;76041 | chr2:178534182;178534181;178534180 | chr2:179398909;179398908;179398907 |
| 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 | rs542891030  |
-0.766 | 0.852 | N | 0.415 | 0.139 | 0.452546404249 | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.78242E-04 | None | 0 | None | 0 | 0 | 0 |
| A/T | rs542891030 |
-0.766 | 0.852 | N | 0.415 | 0.139 | 0.452546404249 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 1.92678E-04 | None | 0 | 0 | 0 | 0 | 0 |
| A/T | rs542891030 |
-0.766 | 0.852 | N | 0.415 | 0.139 | 0.452546404249 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| A/T | rs542891030 |
-0.766 | 0.852 | N | 0.415 | 0.139 | 0.452546404249 | gnomAD-4.0.0 | 3.84199E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 7.27343E-05 | None | 0 | 0 | 0 | 0 | 0 |
| A/V | None | None | 0.959 | N | 0.436 | 0.176 | 0.528308644755 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 | 0.5614 | ambiguous | 0.5682 | pathogenic | -0.38 | Destabilizing | 0.999 | D | 0.431 | neutral | None | None | None | None | I |
| A/D | 0.4042 | ambiguous | 0.4691 | ambiguous | -0.831 | Destabilizing | 0.046 | N | 0.341 | neutral | None | None | None | None | I |
| A/E | 0.3666 | ambiguous | 0.3847 | ambiguous | -0.737 | Destabilizing | 0.852 | D | 0.401 | neutral | N | 0.483940233 | None | None | I |
| A/F | 0.4562 | ambiguous | 0.4725 | ambiguous | -0.527 | Destabilizing | 0.997 | D | 0.491 | neutral | None | None | None | None | I |
| A/G | 0.2059 | likely_benign | 0.2104 | benign | -0.999 | Destabilizing | 0.015 | N | 0.099 | neutral | N | 0.480091851 | None | None | I |
| A/H | 0.5402 | ambiguous | 0.5632 | ambiguous | -1.148 | Destabilizing | 0.999 | D | 0.465 | neutral | None | None | None | None | I |
| A/I | 0.3846 | ambiguous | 0.432 | ambiguous | 0.271 | Stabilizing | 0.991 | D | 0.455 | neutral | None | None | None | None | I |
| A/K | 0.5709 | likely_pathogenic | 0.6108 | pathogenic | -0.731 | Destabilizing | 0.939 | D | 0.41 | neutral | None | None | None | None | I |
| A/L | 0.3036 | likely_benign | 0.321 | benign | 0.271 | Stabilizing | 0.969 | D | 0.417 | neutral | None | None | None | None | I |
| A/M | 0.331 | likely_benign | 0.3453 | ambiguous | 0.208 | Stabilizing | 0.999 | D | 0.433 | neutral | None | None | None | None | I |
| A/N | 0.3546 | ambiguous | 0.3572 | ambiguous | -0.711 | Destabilizing | 0.939 | D | 0.415 | neutral | None | None | None | None | I |
| A/P | 0.9073 | likely_pathogenic | 0.8409 | pathogenic | 0.014 | Stabilizing | 0.988 | D | 0.439 | neutral | D | 0.536638567 | None | None | I |
| A/Q | 0.4337 | ambiguous | 0.4344 | ambiguous | -0.654 | Destabilizing | 0.991 | D | 0.46 | neutral | None | None | None | None | I |
| A/R | 0.4693 | ambiguous | 0.4685 | ambiguous | -0.678 | Destabilizing | 0.991 | D | 0.455 | neutral | None | None | None | None | I |
| A/S | 0.11 | likely_benign | 0.1082 | benign | -1.157 | Destabilizing | 0.31 | N | 0.239 | neutral | N | 0.492405 | None | None | I |
| A/T | 0.11 | likely_benign | 0.1249 | benign | -0.938 | Destabilizing | 0.852 | D | 0.415 | neutral | N | 0.464314322 | None | None | I |
| A/V | 0.1918 | likely_benign | 0.2134 | benign | 0.014 | Stabilizing | 0.959 | D | 0.436 | neutral | N | 0.425078356 | None | None | I |
| A/W | 0.8607 | likely_pathogenic | 0.8342 | pathogenic | -1.081 | Destabilizing | 0.999 | D | 0.59 | neutral | None | None | None | None | I |
| A/Y | 0.5998 | likely_pathogenic | 0.5933 | pathogenic | -0.511 | Destabilizing | 0.997 | D | 0.492 | neutral | 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.