Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15085 | 45478;45479;45480 | chr2:178621571;178621570;178621569 | chr2:179486298;179486297;179486296 |
| N2AB | 13444 | 40555;40556;40557 | chr2:178621571;178621570;178621569 | chr2:179486298;179486297;179486296 |
| N2A | 12517 | 37774;37775;37776 | chr2:178621571;178621570;178621569 | chr2:179486298;179486297;179486296 |
| N2B | 6020 | 18283;18284;18285 | chr2:178621571;178621570;178621569 | chr2:179486298;179486297;179486296 |
| Novex-1 | 6145 | 18658;18659;18660 | chr2:178621571;178621570;178621569 | chr2:179486298;179486297;179486296 |
| Novex-2 | 6212 | 18859;18860;18861 | chr2:178621571;178621570;178621569 | chr2:179486298;179486297;179486296 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/S | rs749903521  |
None | 1.0 | N | 0.759 | 0.385 | 0.346992582518 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/S | rs749903521 |
None | 1.0 | N | 0.759 | 0.385 | 0.346992582518 | gnomAD-4.0.0 | 3.84987E-06 | None | None | None | None | N | None | 5.08509E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/T | rs542139839 |
-1.981 | 1.0 | D | 0.756 | 0.414 | 0.551051292539 | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | N | None | 1.65508E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/T | rs542139839 |
-1.981 | 1.0 | D | 0.756 | 0.414 | 0.551051292539 | gnomAD-3.1.2 | 1.98E-05 | None | None | None | None | N | None | 7.25E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/T | rs542139839 |
-1.981 | 1.0 | D | 0.756 | 0.414 | 0.551051292539 | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 1.5E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/T | rs542139839 |
-1.981 | 1.0 | D | 0.756 | 0.414 | 0.551051292539 | gnomAD-4.0.0 | 7.69841E-06 | None | None | None | None | N | None | 8.45451E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 2.84835E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.7977 | likely_pathogenic | 0.775 | pathogenic | -1.827 | Destabilizing | 0.999 | D | 0.674 | neutral | None | None | None | None | N |
| R/C | 0.2953 | likely_benign | 0.3041 | benign | -2.026 | Highly Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | N |
| R/D | 0.9491 | likely_pathogenic | 0.9517 | pathogenic | -1.2 | Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | N |
| R/E | 0.7515 | likely_pathogenic | 0.7382 | pathogenic | -0.996 | Destabilizing | 0.999 | D | 0.583 | neutral | None | None | None | None | N |
| R/F | 0.8726 | likely_pathogenic | 0.9111 | pathogenic | -1.223 | Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | N |
| R/G | 0.6662 | likely_pathogenic | 0.6219 | pathogenic | -2.16 | Highly Destabilizing | 1.0 | D | 0.781 | deleterious | D | 0.632874756 | None | None | N |
| R/H | 0.1848 | likely_benign | 0.224 | benign | -2.096 | Highly Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | N |
| R/I | 0.5987 | likely_pathogenic | 0.6124 | pathogenic | -0.875 | Destabilizing | 1.0 | D | 0.851 | deleterious | D | 0.602384574 | None | None | N |
| R/K | 0.2553 | likely_benign | 0.2392 | benign | -1.507 | Destabilizing | 0.997 | D | 0.63 | neutral | D | 0.692156625 | None | None | N |
| R/L | 0.5827 | likely_pathogenic | 0.6109 | pathogenic | -0.875 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | N |
| R/M | 0.6062 | likely_pathogenic | 0.5953 | pathogenic | -1.374 | Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | N |
| R/N | 0.8365 | likely_pathogenic | 0.8527 | pathogenic | -1.527 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| R/P | 0.9847 | likely_pathogenic | 0.983 | pathogenic | -1.18 | Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | N |
| R/Q | 0.1737 | likely_benign | 0.1744 | benign | -1.36 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| R/S | 0.8374 | likely_pathogenic | 0.8191 | pathogenic | -2.307 | Highly Destabilizing | 1.0 | D | 0.759 | deleterious | N | 0.498108086 | None | None | N |
| R/T | 0.6506 | likely_pathogenic | 0.6134 | pathogenic | -1.894 | Destabilizing | 1.0 | D | 0.756 | deleterious | D | 0.541187581 | None | None | N |
| R/V | 0.6737 | likely_pathogenic | 0.6801 | pathogenic | -1.18 | Destabilizing | 1.0 | D | 0.838 | deleterious | None | None | None | None | N |
| R/W | 0.3623 | ambiguous | 0.4587 | ambiguous | -0.858 | Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| R/Y | 0.5892 | likely_pathogenic | 0.7069 | pathogenic | -0.631 | Destabilizing | 1.0 | D | 0.852 | deleterious | 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.