Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27009 | 81250;81251;81252 | chr2:178565107;178565106;178565105 | chr2:179429834;179429833;179429832 |
| N2AB | 25368 | 76327;76328;76329 | chr2:178565107;178565106;178565105 | chr2:179429834;179429833;179429832 |
| N2A | 24441 | 73546;73547;73548 | chr2:178565107;178565106;178565105 | chr2:179429834;179429833;179429832 |
| N2B | 17944 | 54055;54056;54057 | chr2:178565107;178565106;178565105 | chr2:179429834;179429833;179429832 |
| Novex-1 | 18069 | 54430;54431;54432 | chr2:178565107;178565106;178565105 | chr2:179429834;179429833;179429832 |
| Novex-2 | 18136 | 54631;54632;54633 | chr2:178565107;178565106;178565105 | chr2:179429834;179429833;179429832 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/F | None | None | 0.942 | N | 0.681 | 0.338 | 0.566846708062 | gnomAD-4.0.0 | 1.5918E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85935E-06 | 0 | 0 |
| I/S | None | None | 0.942 | N | 0.65 | 0.486 | 0.738858788324 | gnomAD-4.0.0 | 1.5918E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85932E-06 | 0 | 0 |
| I/T | rs1408591294  |
-2.993 | 0.822 | N | 0.676 | 0.429 | 0.645206814577 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs1408591294 |
-2.993 | 0.822 | N | 0.676 | 0.429 | 0.645206814577 | gnomAD-4.0.0 | 1.5918E-06 | None | None | None | None | N | None | 0 | 2.28666E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs763457498 |
-1.819 | 0.006 | N | 0.245 | 0.088 | 0.399740851666 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 8.9E-06 | 0 |
| I/V | rs763457498 |
-1.819 | 0.006 | N | 0.245 | 0.088 | 0.399740851666 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.93274E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs763457498 |
-1.819 | 0.006 | N | 0.245 | 0.088 | 0.399740851666 | gnomAD-4.0.0 | 5.12593E-06 | None | None | None | None | N | None | 0 | 1.69526E-05 | None | 0 | 4.85225E-05 | None | 0 | 0 | 2.3938E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.52 | ambiguous | 0.4641 | ambiguous | -3.007 | Highly Destabilizing | 0.754 | D | 0.662 | neutral | None | None | None | None | N |
| I/C | 0.7935 | likely_pathogenic | 0.7568 | pathogenic | -2.295 | Highly Destabilizing | 0.998 | D | 0.701 | prob.neutral | None | None | None | None | N |
| I/D | 0.9602 | likely_pathogenic | 0.9599 | pathogenic | -3.52 | Highly Destabilizing | 0.993 | D | 0.782 | deleterious | None | None | None | None | N |
| I/E | 0.8933 | likely_pathogenic | 0.8879 | pathogenic | -3.309 | Highly Destabilizing | 0.978 | D | 0.754 | deleterious | None | None | None | None | N |
| I/F | 0.3888 | ambiguous | 0.3673 | ambiguous | -1.811 | Destabilizing | 0.942 | D | 0.681 | prob.neutral | N | 0.477191681 | None | None | N |
| I/G | 0.9056 | likely_pathogenic | 0.8808 | pathogenic | -3.518 | Highly Destabilizing | 0.978 | D | 0.755 | deleterious | None | None | None | None | N |
| I/H | 0.7651 | likely_pathogenic | 0.7685 | pathogenic | -2.85 | Highly Destabilizing | 0.998 | D | 0.769 | deleterious | None | None | None | None | N |
| I/K | 0.7577 | likely_pathogenic | 0.7628 | pathogenic | -2.405 | Highly Destabilizing | 0.978 | D | 0.752 | deleterious | None | None | None | None | N |
| I/L | 0.2467 | likely_benign | 0.2107 | benign | -1.513 | Destabilizing | 0.294 | N | 0.473 | neutral | N | 0.47098671 | None | None | N |
| I/M | 0.178 | likely_benign | 0.1464 | benign | -1.47 | Destabilizing | 0.942 | D | 0.689 | prob.neutral | N | 0.497537662 | None | None | N |
| I/N | 0.6322 | likely_pathogenic | 0.6334 | pathogenic | -2.758 | Highly Destabilizing | 0.99 | D | 0.807 | deleterious | N | 0.486115224 | None | None | N |
| I/P | 0.9916 | likely_pathogenic | 0.991 | pathogenic | -1.997 | Destabilizing | 0.993 | D | 0.795 | deleterious | None | None | None | None | N |
| I/Q | 0.7611 | likely_pathogenic | 0.7452 | pathogenic | -2.652 | Highly Destabilizing | 0.993 | D | 0.799 | deleterious | None | None | None | None | N |
| I/R | 0.6283 | likely_pathogenic | 0.6364 | pathogenic | -1.958 | Destabilizing | 0.978 | D | 0.805 | deleterious | None | None | None | None | N |
| I/S | 0.4889 | ambiguous | 0.4538 | ambiguous | -3.401 | Highly Destabilizing | 0.942 | D | 0.65 | neutral | N | 0.464933096 | None | None | N |
| I/T | 0.2275 | likely_benign | 0.2022 | benign | -3.064 | Highly Destabilizing | 0.822 | D | 0.676 | prob.neutral | N | 0.496218018 | None | None | N |
| I/V | 0.0758 | likely_benign | 0.0664 | benign | -1.997 | Destabilizing | 0.006 | N | 0.245 | neutral | N | 0.471053001 | None | None | N |
| I/W | 0.9281 | likely_pathogenic | 0.9243 | pathogenic | -2.216 | Highly Destabilizing | 0.998 | D | 0.733 | prob.delet. | None | None | None | None | N |
| I/Y | 0.7798 | likely_pathogenic | 0.7777 | pathogenic | -2.035 | Highly Destabilizing | 0.978 | D | 0.701 | prob.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.