Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30121 | 90586;90587;90588 | chr2:178552539;178552538;178552537 | chr2:179417266;179417265;179417264 |
| N2AB | 28480 | 85663;85664;85665 | chr2:178552539;178552538;178552537 | chr2:179417266;179417265;179417264 |
| N2A | 27553 | 82882;82883;82884 | chr2:178552539;178552538;178552537 | chr2:179417266;179417265;179417264 |
| N2B | 21056 | 63391;63392;63393 | chr2:178552539;178552538;178552537 | chr2:179417266;179417265;179417264 |
| Novex-1 | 21181 | 63766;63767;63768 | chr2:178552539;178552538;178552537 | chr2:179417266;179417265;179417264 |
| Novex-2 | 21248 | 63967;63968;63969 | chr2:178552539;178552538;178552537 | chr2:179417266;179417265;179417264 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs1028805894  |
None | 0.991 | N | 0.51 | 0.153 | 0.17258766438 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| T/A | rs1028805894 |
None | 0.991 | N | 0.51 | 0.153 | 0.17258766438 | gnomAD-4.0.0 | 4.33788E-06 | None | None | None | None | N | None | 0 | 1.667E-05 | None | 0 | 0 | None | 0 | 0 | 5.08563E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0985 | likely_benign | 0.0926 | benign | -0.607 | Destabilizing | 0.991 | D | 0.51 | neutral | N | 0.462553239 | None | None | N |
| T/C | 0.4355 | ambiguous | 0.427 | ambiguous | -0.426 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| T/D | 0.4926 | ambiguous | 0.4421 | ambiguous | 0.224 | Stabilizing | 0.998 | D | 0.64 | neutral | None | None | None | None | N |
| T/E | 0.3135 | likely_benign | 0.2945 | benign | 0.207 | Stabilizing | 0.987 | D | 0.672 | prob.neutral | None | None | None | None | N |
| T/F | 0.2958 | likely_benign | 0.2527 | benign | -0.724 | Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | N |
| T/G | 0.4539 | ambiguous | 0.4215 | ambiguous | -0.838 | Destabilizing | 0.999 | D | 0.603 | neutral | None | None | None | None | N |
| T/H | 0.32 | likely_benign | 0.2758 | benign | -1.064 | Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| T/I | 0.1233 | likely_benign | 0.1131 | benign | -0.097 | Destabilizing | 1.0 | D | 0.729 | deleterious | N | 0.394072298 | None | None | N |
| T/K | 0.2852 | likely_benign | 0.2385 | benign | -0.528 | Destabilizing | 0.983 | D | 0.674 | prob.neutral | N | 0.462806728 | None | None | N |
| T/L | 0.0999 | likely_benign | 0.0937 | benign | -0.097 | Destabilizing | 0.997 | D | 0.67 | prob.neutral | None | None | None | None | N |
| T/M | 0.0867 | likely_benign | 0.0871 | benign | 0.054 | Stabilizing | 1.0 | D | 0.735 | deleterious | None | None | None | None | N |
| T/N | 0.156 | likely_benign | 0.1465 | benign | -0.414 | Destabilizing | 0.999 | D | 0.62 | neutral | None | None | None | None | N |
| T/P | 0.1901 | likely_benign | 0.1541 | benign | -0.235 | Destabilizing | 1.0 | D | 0.72 | deleterious | N | 0.463820687 | None | None | N |
| T/Q | 0.255 | likely_benign | 0.2392 | benign | -0.581 | Destabilizing | 0.931 | D | 0.497 | neutral | None | None | None | None | N |
| T/R | 0.2469 | likely_benign | 0.2019 | benign | -0.302 | Destabilizing | 0.997 | D | 0.707 | prob.delet. | N | 0.463060218 | None | None | N |
| T/S | 0.1564 | likely_benign | 0.15 | benign | -0.732 | Destabilizing | 0.991 | D | 0.529 | neutral | N | 0.461032302 | None | None | N |
| T/V | 0.1088 | likely_benign | 0.1079 | benign | -0.235 | Destabilizing | 0.997 | D | 0.634 | neutral | None | None | None | None | N |
| T/W | 0.6687 | likely_pathogenic | 0.612 | pathogenic | -0.654 | Destabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | N |
| T/Y | 0.3175 | likely_benign | 0.2866 | benign | -0.415 | Destabilizing | 1.0 | D | 0.816 | 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.