Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26055 | 78388;78389;78390 | chr2:178567969;178567968;178567967 | chr2:179432696;179432695;179432694 |
| N2AB | 24414 | 73465;73466;73467 | chr2:178567969;178567968;178567967 | chr2:179432696;179432695;179432694 |
| N2A | 23487 | 70684;70685;70686 | chr2:178567969;178567968;178567967 | chr2:179432696;179432695;179432694 |
| N2B | 16990 | 51193;51194;51195 | chr2:178567969;178567968;178567967 | chr2:179432696;179432695;179432694 |
| Novex-1 | 17115 | 51568;51569;51570 | chr2:178567969;178567968;178567967 | chr2:179432696;179432695;179432694 |
| Novex-2 | 17182 | 51769;51770;51771 | chr2:178567969;178567968;178567967 | chr2:179432696;179432695;179432694 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/I | rs765696931  |
-1.517 | 0.999 | D | 0.828 | 0.708 | 0.796922635108 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| L/I | rs765696931 |
-1.517 | 0.999 | D | 0.828 | 0.708 | 0.796922635108 | gnomAD-4.0.0 | 6.84311E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.1595E-05 | 0 |
| L/V | rs765696931 |
-2.042 | 0.999 | D | 0.831 | 0.699 | 0.779834127323 | 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 |
| L/V | rs765696931 |
-2.042 | 0.999 | D | 0.831 | 0.699 | 0.779834127323 | gnomAD-4.0.0 | 4.79018E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.39748E-06 | 0 | 1.65717E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9071 | likely_pathogenic | 0.9263 | pathogenic | -2.671 | Highly Destabilizing | 0.999 | D | 0.826 | deleterious | None | None | None | None | N |
| L/C | 0.8669 | likely_pathogenic | 0.8564 | pathogenic | -2.365 | Highly Destabilizing | 1.0 | D | 0.792 | deleterious | None | None | None | None | N |
| L/D | 0.9983 | likely_pathogenic | 0.9983 | pathogenic | -3.315 | Highly Destabilizing | 1.0 | D | 0.856 | deleterious | None | None | None | None | N |
| L/E | 0.9906 | likely_pathogenic | 0.9916 | pathogenic | -3.152 | Highly Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| L/F | 0.6082 | likely_pathogenic | 0.6048 | pathogenic | -1.782 | Destabilizing | 1.0 | D | 0.869 | deleterious | D | 0.651046363 | None | None | N |
| L/G | 0.9827 | likely_pathogenic | 0.9849 | pathogenic | -3.168 | Highly Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | N |
| L/H | 0.9779 | likely_pathogenic | 0.9771 | pathogenic | -2.544 | Highly Destabilizing | 1.0 | D | 0.806 | deleterious | D | 0.667872941 | None | None | N |
| L/I | 0.2429 | likely_benign | 0.2802 | benign | -1.253 | Destabilizing | 0.999 | D | 0.828 | deleterious | D | 0.617998619 | None | None | N |
| L/K | 0.9865 | likely_pathogenic | 0.988 | pathogenic | -2.116 | Highly Destabilizing | 1.0 | D | 0.842 | deleterious | None | None | None | None | N |
| L/M | 0.2618 | likely_benign | 0.2622 | benign | -1.261 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| L/N | 0.9882 | likely_pathogenic | 0.9881 | pathogenic | -2.418 | Highly Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | N |
| L/P | 0.9871 | likely_pathogenic | 0.9899 | pathogenic | -1.706 | Destabilizing | 1.0 | D | 0.853 | deleterious | D | 0.667872941 | None | None | N |
| L/Q | 0.9625 | likely_pathogenic | 0.965 | pathogenic | -2.402 | Highly Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| L/R | 0.9732 | likely_pathogenic | 0.9759 | pathogenic | -1.65 | Destabilizing | 1.0 | D | 0.847 | deleterious | D | 0.65185358 | None | None | N |
| L/S | 0.98 | likely_pathogenic | 0.9828 | pathogenic | -3.073 | Highly Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| L/T | 0.8912 | likely_pathogenic | 0.9101 | pathogenic | -2.77 | Highly Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | N |
| L/V | 0.2948 | likely_benign | 0.3387 | benign | -1.706 | Destabilizing | 0.999 | D | 0.831 | deleterious | D | 0.560996838 | None | None | N |
| L/W | 0.9351 | likely_pathogenic | 0.9382 | pathogenic | -2.141 | Highly Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| L/Y | 0.9558 | likely_pathogenic | 0.9557 | pathogenic | -1.903 | Destabilizing | 1.0 | D | 0.825 | 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.