Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16417 | 49474;49475;49476 | chr2:178614148;178614147;178614146 | chr2:179478875;179478874;179478873 |
| N2AB | 14776 | 44551;44552;44553 | chr2:178614148;178614147;178614146 | chr2:179478875;179478874;179478873 |
| N2A | 13849 | 41770;41771;41772 | chr2:178614148;178614147;178614146 | chr2:179478875;179478874;179478873 |
| N2B | 7352 | 22279;22280;22281 | chr2:178614148;178614147;178614146 | chr2:179478875;179478874;179478873 |
| Novex-1 | 7477 | 22654;22655;22656 | chr2:178614148;178614147;178614146 | chr2:179478875;179478874;179478873 |
| Novex-2 | 7544 | 22855;22856;22857 | chr2:178614148;178614147;178614146 | chr2:179478875;179478874;179478873 |
| 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/R | rs1387631926  |
-0.593 | 0.852 | D | 0.475 | 0.49 | 0.593114555169 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| P/R | rs1387631926 |
-0.593 | 0.852 | D | 0.475 | 0.49 | 0.593114555169 | gnomAD-4.0.0 | 1.59407E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43361E-05 | 0 |
| P/S | None | None | 0.852 | D | 0.335 | 0.41 | 0.344017737713 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 6.07533E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0859 | likely_benign | 0.0779 | benign | -1.23 | Destabilizing | 0.061 | N | 0.168 | neutral | N | 0.501930981 | None | None | N |
| P/C | 0.5772 | likely_pathogenic | 0.528 | ambiguous | -0.771 | Destabilizing | 0.999 | D | 0.515 | neutral | None | None | None | None | N |
| P/D | 0.767 | likely_pathogenic | 0.7076 | pathogenic | -1.251 | Destabilizing | 0.969 | D | 0.435 | neutral | None | None | None | None | N |
| P/E | 0.4272 | ambiguous | 0.3722 | ambiguous | -1.333 | Destabilizing | 0.939 | D | 0.396 | neutral | None | None | None | None | N |
| P/F | 0.738 | likely_pathogenic | 0.663 | pathogenic | -1.23 | Destabilizing | 0.997 | D | 0.543 | neutral | None | None | None | None | N |
| P/G | 0.4238 | ambiguous | 0.3736 | ambiguous | -1.45 | Destabilizing | 0.884 | D | 0.353 | neutral | None | None | None | None | N |
| P/H | 0.3754 | ambiguous | 0.3247 | benign | -0.976 | Destabilizing | 0.999 | D | 0.464 | neutral | D | 0.630857214 | None | None | N |
| P/I | 0.5112 | ambiguous | 0.4267 | ambiguous | -0.761 | Destabilizing | 0.991 | D | 0.54 | neutral | None | None | None | None | N |
| P/K | 0.4864 | ambiguous | 0.4001 | ambiguous | -1.102 | Destabilizing | 0.079 | N | 0.187 | neutral | None | None | None | None | N |
| P/L | 0.2362 | likely_benign | 0.1931 | benign | -0.761 | Destabilizing | 0.92 | D | 0.498 | neutral | D | 0.629940803 | None | None | N |
| P/M | 0.4914 | ambiguous | 0.4254 | ambiguous | -0.475 | Destabilizing | 0.999 | D | 0.469 | neutral | None | None | None | None | N |
| P/N | 0.5593 | ambiguous | 0.4996 | ambiguous | -0.775 | Destabilizing | 0.991 | D | 0.494 | neutral | None | None | None | None | N |
| P/Q | 0.226 | likely_benign | 0.1919 | benign | -1.065 | Destabilizing | 0.982 | D | 0.449 | neutral | None | None | None | None | N |
| P/R | 0.3558 | ambiguous | 0.2833 | benign | -0.427 | Destabilizing | 0.852 | D | 0.475 | neutral | D | 0.589310285 | None | None | N |
| P/S | 0.1841 | likely_benign | 0.1623 | benign | -1.153 | Destabilizing | 0.852 | D | 0.335 | neutral | D | 0.582495722 | None | None | N |
| P/T | 0.163 | likely_benign | 0.1392 | benign | -1.141 | Destabilizing | 0.92 | D | 0.384 | neutral | N | 0.507032417 | None | None | N |
| P/V | 0.3416 | ambiguous | 0.2788 | benign | -0.883 | Destabilizing | 0.939 | D | 0.44 | neutral | None | None | None | None | N |
| P/W | 0.856 | likely_pathogenic | 0.7911 | pathogenic | -1.327 | Destabilizing | 0.999 | D | 0.581 | neutral | None | None | None | None | N |
| P/Y | 0.6901 | likely_pathogenic | 0.6147 | pathogenic | -1.073 | Destabilizing | 0.997 | D | 0.539 | 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.