Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13877 | 41854;41855;41856 | chr2:178635695;178635694;178635693 | chr2:179500422;179500421;179500420 |
| N2AB | 12236 | 36931;36932;36933 | chr2:178635695;178635694;178635693 | chr2:179500422;179500421;179500420 |
| N2A | 11309 | 34150;34151;34152 | chr2:178635695;178635694;178635693 | chr2:179500422;179500421;179500420 |
| N2B | 4812 | 14659;14660;14661 | chr2:178635695;178635694;178635693 | chr2:179500422;179500421;179500420 |
| Novex-1 | 4937 | 15034;15035;15036 | chr2:178635695;178635694;178635693 | chr2:179500422;179500421;179500420 |
| Novex-2 | 5004 | 15235;15236;15237 | chr2:178635695;178635694;178635693 | chr2:179500422;179500421;179500420 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs199969810  |
None | 0.132 | D | 0.252 | 0.185 | 0.354183961838 | gnomAD-4.0.0 | 1.63166E-06 | None | None | None | None | N | None | 0 | 2.40408E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/G | rs199969810 |
-1.56 | 0.919 | D | 0.556 | 0.27 | None | gnomAD-4.0.0 | 2.87175E-04 | None | None | None | None | N | None | 1.15141E-04 | 2.40419E-05 | None | 0 | 1.1318E-04 | None | 2.9905E-03 | 0 | 2.62548E-05 | 0 | 2.15637E-04 |
| V/M | rs1272825852 |
-0.329 | 0.996 | D | 0.523 | 0.289 | 0.410603549233 | gnomAD-2.1.1 | 4.36E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.58E-05 | None | 0 | 0 | 0 |
| V/M | rs1272825852 |
-0.329 | 0.996 | D | 0.523 | 0.289 | 0.410603549233 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.079E-04 | 0 |
| V/M | rs1272825852 |
-0.329 | 0.996 | D | 0.523 | 0.289 | 0.410603549233 | gnomAD-4.0.0 | 3.90504E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.45483E-05 | None | 0 | 0 | 0 | 2.76068E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.4064 | ambiguous | 0.5735 | pathogenic | -0.344 | Destabilizing | 0.132 | N | 0.252 | neutral | D | 0.523737891 | None | None | N |
| V/C | 0.8691 | likely_pathogenic | 0.9063 | pathogenic | -0.559 | Destabilizing | 0.999 | D | 0.571 | neutral | None | None | None | None | N |
| V/D | 0.8174 | likely_pathogenic | 0.9024 | pathogenic | -0.401 | Destabilizing | 0.991 | D | 0.748 | deleterious | None | None | None | None | N |
| V/E | 0.5643 | likely_pathogenic | 0.6989 | pathogenic | -0.523 | Destabilizing | 0.988 | D | 0.531 | neutral | D | 0.523932602 | None | None | N |
| V/F | 0.4437 | ambiguous | 0.538 | ambiguous | -0.649 | Destabilizing | 0.997 | D | 0.503 | neutral | None | None | None | None | N |
| V/G | 0.4413 | ambiguous | 0.6312 | pathogenic | -0.45 | Destabilizing | 0.919 | D | 0.556 | neutral | D | 0.526869812 | None | None | N |
| V/H | 0.8136 | likely_pathogenic | 0.8839 | pathogenic | -0.043 | Destabilizing | 0.999 | D | 0.756 | deleterious | None | None | None | None | N |
| V/I | 0.0995 | likely_benign | 0.1051 | benign | -0.215 | Destabilizing | 0.938 | D | 0.489 | neutral | None | None | None | None | N |
| V/K | 0.5124 | ambiguous | 0.6209 | pathogenic | -0.391 | Destabilizing | 0.981 | D | 0.563 | neutral | None | None | None | None | N |
| V/L | 0.3025 | likely_benign | 0.3885 | ambiguous | -0.215 | Destabilizing | 0.824 | D | 0.502 | neutral | N | 0.441787814 | None | None | N |
| V/M | 0.2934 | likely_benign | 0.3909 | ambiguous | -0.368 | Destabilizing | 0.996 | D | 0.523 | neutral | D | 0.526869812 | None | None | N |
| V/N | 0.6039 | likely_pathogenic | 0.7237 | pathogenic | -0.099 | Destabilizing | 0.991 | D | 0.759 | deleterious | None | None | None | None | N |
| V/P | 0.9087 | likely_pathogenic | 0.949 | pathogenic | -0.225 | Destabilizing | 0.991 | D | 0.725 | deleterious | None | None | None | None | N |
| V/Q | 0.4615 | ambiguous | 0.5709 | pathogenic | -0.357 | Destabilizing | 0.997 | D | 0.733 | deleterious | None | None | None | None | N |
| V/R | 0.4864 | ambiguous | 0.5895 | pathogenic | 0.128 | Stabilizing | 0.991 | D | 0.751 | deleterious | None | None | None | None | N |
| V/S | 0.4882 | ambiguous | 0.6366 | pathogenic | -0.402 | Destabilizing | 0.883 | D | 0.507 | neutral | None | None | None | None | N |
| V/T | 0.3507 | ambiguous | 0.4751 | ambiguous | -0.43 | Destabilizing | 0.168 | N | 0.311 | neutral | None | None | None | None | N |
| V/W | 0.9462 | likely_pathogenic | 0.9654 | pathogenic | -0.73 | Destabilizing | 0.999 | D | 0.765 | deleterious | None | None | None | None | N |
| V/Y | 0.8141 | likely_pathogenic | 0.867 | pathogenic | -0.429 | Destabilizing | 0.997 | D | 0.518 | neutral | None | None | 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.