Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15781 | 47566;47567;47568 | chr2:178618010;178618009;178618008 | chr2:179482737;179482736;179482735 |
| N2AB | 14140 | 42643;42644;42645 | chr2:178618010;178618009;178618008 | chr2:179482737;179482736;179482735 |
| N2A | 13213 | 39862;39863;39864 | chr2:178618010;178618009;178618008 | chr2:179482737;179482736;179482735 |
| N2B | 6716 | 20371;20372;20373 | chr2:178618010;178618009;178618008 | chr2:179482737;179482736;179482735 |
| Novex-1 | 6841 | 20746;20747;20748 | chr2:178618010;178618009;178618008 | chr2:179482737;179482736;179482735 |
| Novex-2 | 6908 | 20947;20948;20949 | chr2:178618010;178618009;178618008 | chr2:179482737;179482736;179482735 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | rs932333848  |
None | 0.026 | N | 0.355 | 0.243 | 0.255270683199 | gnomAD-4.0.0 | 8.21618E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 3.03674E-04 | None | 0 | 0 | 0 | 0 | 0 |
| P/Q | rs756745318 |
-1.811 | 0.968 | D | 0.662 | 0.386 | 0.448794319169 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| P/Q | rs756745318 |
-1.811 | 0.968 | D | 0.662 | 0.386 | 0.448794319169 | gnomAD-4.0.0 | 1.59381E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8627E-06 | 0 | 0 |
| P/T | rs932333848 |
None | 0.896 | D | 0.579 | 0.376 | 0.450152462452 | gnomAD-4.0.0 | 6.84682E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.53062E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0717 | likely_benign | 0.0708 | benign | -1.86 | Destabilizing | 0.026 | N | 0.355 | neutral | N | 0.48815135 | None | None | N |
| P/C | 0.5268 | ambiguous | 0.468 | ambiguous | -1.219 | Destabilizing | 0.999 | D | 0.737 | prob.delet. | None | None | None | None | N |
| P/D | 0.5709 | likely_pathogenic | 0.5426 | ambiguous | -2.219 | Highly Destabilizing | 0.851 | D | 0.58 | neutral | None | None | None | None | N |
| P/E | 0.2231 | likely_benign | 0.2202 | benign | -2.086 | Highly Destabilizing | 0.261 | N | 0.365 | neutral | None | None | None | None | N |
| P/F | 0.5108 | ambiguous | 0.4743 | ambiguous | -1.259 | Destabilizing | 0.988 | D | 0.744 | deleterious | None | None | None | None | N |
| P/G | 0.3876 | ambiguous | 0.3658 | ambiguous | -2.265 | Highly Destabilizing | 0.851 | D | 0.605 | neutral | None | None | None | None | N |
| P/H | 0.2264 | likely_benign | 0.2169 | benign | -1.666 | Destabilizing | 0.999 | D | 0.712 | prob.delet. | None | None | None | None | N |
| P/I | 0.2174 | likely_benign | 0.1952 | benign | -0.774 | Destabilizing | 0.976 | D | 0.733 | prob.delet. | None | None | None | None | N |
| P/K | 0.1339 | likely_benign | 0.1358 | benign | -1.639 | Destabilizing | 0.851 | D | 0.519 | neutral | None | None | None | None | N |
| P/L | 0.1096 | likely_benign | 0.1054 | benign | -0.774 | Destabilizing | 0.968 | D | 0.669 | neutral | D | 0.663779194 | None | None | N |
| P/M | 0.251 | likely_benign | 0.2282 | benign | -0.67 | Destabilizing | 0.999 | D | 0.709 | prob.delet. | None | None | None | None | N |
| P/N | 0.4338 | ambiguous | 0.4009 | ambiguous | -1.744 | Destabilizing | 0.988 | D | 0.703 | prob.neutral | None | None | None | None | N |
| P/Q | 0.1259 | likely_benign | 0.1242 | benign | -1.758 | Destabilizing | 0.968 | D | 0.662 | neutral | D | 0.567499926 | None | None | N |
| P/R | 0.103 | likely_benign | 0.1073 | benign | -1.225 | Destabilizing | 0.059 | N | 0.497 | neutral | N | 0.493309501 | None | None | N |
| P/S | 0.1658 | likely_benign | 0.1581 | benign | -2.255 | Highly Destabilizing | 0.811 | D | 0.54 | neutral | D | 0.562569047 | None | None | N |
| P/T | 0.1291 | likely_benign | 0.1214 | benign | -1.997 | Destabilizing | 0.896 | D | 0.579 | neutral | D | 0.601202764 | None | None | N |
| P/V | 0.1479 | likely_benign | 0.1364 | benign | -1.108 | Destabilizing | 0.952 | D | 0.643 | neutral | None | None | None | None | N |
| P/W | 0.7317 | likely_pathogenic | 0.7059 | pathogenic | -1.568 | Destabilizing | 0.999 | D | 0.705 | prob.neutral | None | None | None | None | N |
| P/Y | 0.4878 | ambiguous | 0.457 | ambiguous | -1.228 | Destabilizing | 0.996 | D | 0.745 | 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.