Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13851 | 41776;41777;41778 | chr2:178636020;178636019;178636018 | chr2:179500747;179500746;179500745 |
| N2AB | 12210 | 36853;36854;36855 | chr2:178636020;178636019;178636018 | chr2:179500747;179500746;179500745 |
| N2A | 11283 | 34072;34073;34074 | chr2:178636020;178636019;178636018 | chr2:179500747;179500746;179500745 |
| N2B | 4786 | 14581;14582;14583 | chr2:178636020;178636019;178636018 | chr2:179500747;179500746;179500745 |
| Novex-1 | 4911 | 14956;14957;14958 | chr2:178636020;178636019;178636018 | chr2:179500747;179500746;179500745 |
| Novex-2 | 4978 | 15157;15158;15159 | chr2:178636020;178636019;178636018 | chr2:179500747;179500746;179500745 |
| 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 | rs1346163990  |
-1.347 | 0.552 | N | 0.551 | 0.205 | 0.218845423259 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 1.14811E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/A | rs1346163990 |
-1.347 | 0.552 | N | 0.551 | 0.205 | 0.218845423259 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/A | rs1346163990 |
-1.347 | 0.552 | N | 0.551 | 0.205 | 0.218845423259 | gnomAD-4.0.0 | 6.57514E-06 | None | None | None | None | N | None | 2.41289E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/P | rs1346163990 |
-0.798 | 0.977 | N | 0.713 | 0.273 | 0.312306559268 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| T/R | rs1282841965 |
-0.413 | 0.954 | N | 0.721 | 0.341 | 0.347659731818 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 8.92E-06 | 0 |
| T/R | rs1282841965 |
-0.413 | 0.954 | N | 0.721 | 0.341 | 0.347659731818 | gnomAD-4.0.0 | 3.18665E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86228E-06 | 1.43447E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.2483 | likely_benign | 0.2286 | benign | -1.225 | Destabilizing | 0.552 | D | 0.551 | neutral | N | 0.41726595 | None | None | N |
| T/C | 0.6915 | likely_pathogenic | 0.6798 | pathogenic | -1.19 | Destabilizing | 0.998 | D | 0.675 | prob.neutral | None | None | None | None | N |
| T/D | 0.9052 | likely_pathogenic | 0.889 | pathogenic | -1.476 | Destabilizing | 0.888 | D | 0.671 | prob.neutral | None | None | None | None | N |
| T/E | 0.7613 | likely_pathogenic | 0.7283 | pathogenic | -1.354 | Destabilizing | 0.888 | D | 0.685 | prob.delet. | None | None | None | None | N |
| T/F | 0.6268 | likely_pathogenic | 0.5939 | pathogenic | -1.16 | Destabilizing | 0.994 | D | 0.772 | deleterious | None | None | None | None | N |
| T/G | 0.7525 | likely_pathogenic | 0.7133 | pathogenic | -1.558 | Destabilizing | 0.798 | D | 0.697 | prob.delet. | None | None | None | None | N |
| T/H | 0.5516 | ambiguous | 0.5066 | ambiguous | -1.717 | Destabilizing | 0.998 | D | 0.739 | deleterious | None | None | None | None | N |
| T/I | 0.3944 | ambiguous | 0.3613 | ambiguous | -0.384 | Destabilizing | 0.977 | D | 0.692 | prob.delet. | N | 0.349671428 | None | None | N |
| T/K | 0.4576 | ambiguous | 0.4076 | ambiguous | -0.747 | Destabilizing | 0.856 | D | 0.677 | prob.neutral | N | 0.323563967 | None | None | N |
| T/L | 0.3328 | likely_benign | 0.3021 | benign | -0.384 | Destabilizing | 0.888 | D | 0.661 | prob.neutral | None | None | None | None | N |
| T/M | 0.1699 | likely_benign | 0.1536 | benign | -0.269 | Destabilizing | 0.998 | D | 0.677 | prob.neutral | None | None | None | None | N |
| T/N | 0.4939 | ambiguous | 0.4576 | ambiguous | -1.217 | Destabilizing | 0.888 | D | 0.629 | neutral | None | None | None | None | N |
| T/P | 0.9694 | likely_pathogenic | 0.9639 | pathogenic | -0.634 | Destabilizing | 0.977 | D | 0.713 | prob.delet. | N | 0.476938123 | None | None | N |
| T/Q | 0.5319 | ambiguous | 0.473 | ambiguous | -1.259 | Destabilizing | 0.983 | D | 0.708 | prob.delet. | None | None | None | None | N |
| T/R | 0.3834 | ambiguous | 0.3437 | ambiguous | -0.682 | Destabilizing | 0.954 | D | 0.721 | deleterious | N | 0.32818564 | None | None | N |
| T/S | 0.282 | likely_benign | 0.2679 | benign | -1.455 | Destabilizing | 0.074 | N | 0.328 | neutral | N | 0.335664406 | None | None | N |
| T/V | 0.2704 | likely_benign | 0.2517 | benign | -0.634 | Destabilizing | 0.888 | D | 0.593 | neutral | None | None | None | None | N |
| T/W | 0.8883 | likely_pathogenic | 0.8793 | pathogenic | -1.161 | Destabilizing | 0.998 | D | 0.714 | prob.delet. | None | None | None | None | N |
| T/Y | 0.7142 | likely_pathogenic | 0.672 | pathogenic | -0.828 | Destabilizing | 0.994 | D | 0.765 | 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.