TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24421	73486;73487;73488	chr2:178572871;178572870;178572869	chr2:179437598;179437597;179437596
N2AB	22780	68563;68564;68565	chr2:178572871;178572870;178572869	chr2:179437598;179437597;179437596
N2A	21853	65782;65783;65784	chr2:178572871;178572870;178572869	chr2:179437598;179437597;179437596
N2B	15356	46291;46292;46293	chr2:178572871;178572870;178572869	chr2:179437598;179437597;179437596
Novex-1	15481	46666;46667;46668	chr2:178572871;178572870;178572869	chr2:179437598;179437597;179437596
Novex-2	15548	46867;46868;46869	chr2:178572871;178572870;178572869	chr2:179437598;179437597;179437596
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-65
• Domain position: 99
• Structural Position: 132
• Q(SASA): 0.8754
• Predicted PPI site: N

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
D/E	None	None	0.002	N	0.287	0.05	0.0986583533028	gnomAD-4.0.0	1.59203E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85943E-06	0	0
D/N	None	None	0.693	D	0.761	0.257	0.389283895039	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
D/A	0.3859	ambiguous	0.4032	ambiguous	-0.254	Destabilizing	0.244	N	0.589	neutral	N	0.517876661	None	None	N
D/C	0.853	likely_pathogenic	0.8751	pathogenic	0.182	Stabilizing	0.986	D	0.875	deleterious	None	None	None	None	N
D/E	0.104	likely_benign	0.0913	benign	-0.284	Destabilizing	0.002	N	0.287	neutral	N	0.414152073	None	None	N
D/F	0.862	likely_pathogenic	0.8862	pathogenic	-0.38	Destabilizing	0.986	D	0.796	deleterious	None	None	None	None	N
D/G	0.4527	ambiguous	0.4671	ambiguous	-0.406	Destabilizing	0.392	N	0.711	prob.delet.	N	0.502289328	None	None	N
D/H	0.6951	likely_pathogenic	0.7359	pathogenic	-0.227	Destabilizing	0.945	D	0.81	deleterious	D	0.533827548	None	None	N
D/I	0.6219	likely_pathogenic	0.6625	pathogenic	0.087	Stabilizing	0.858	D	0.805	deleterious	None	None	None	None	N
D/K	0.7175	likely_pathogenic	0.7116	pathogenic	0.459	Stabilizing	0.6	D	0.723	deleterious	None	None	None	None	N
D/L	0.6027	likely_pathogenic	0.6306	pathogenic	0.087	Stabilizing	0.749	D	0.759	deleterious	None	None	None	None	N
D/M	0.7976	likely_pathogenic	0.8145	pathogenic	0.275	Stabilizing	0.986	D	0.859	deleterious	None	None	None	None	N
D/N	0.2363	likely_benign	0.2673	benign	0.25	Stabilizing	0.693	D	0.761	deleterious	D	0.522186403	None	None	N
D/P	0.7994	likely_pathogenic	0.7974	pathogenic	-0.006	Destabilizing	0.858	D	0.783	deleterious	None	None	None	None	N
D/Q	0.5668	likely_pathogenic	0.5887	pathogenic	0.248	Stabilizing	0.6	D	0.797	deleterious	None	None	None	None	N
D/R	0.8009	likely_pathogenic	0.8008	pathogenic	0.506	Stabilizing	0.6	D	0.763	deleterious	None	None	None	None	N
D/S	0.363	ambiguous	0.3948	ambiguous	0.162	Stabilizing	0.299	N	0.709	prob.delet.	None	None	None	None	N
D/T	0.546	ambiguous	0.5718	pathogenic	0.279	Stabilizing	0.749	D	0.763	deleterious	None	None	None	None	N
D/V	0.4162	ambiguous	0.4409	ambiguous	-0.006	Destabilizing	0.693	D	0.759	deleterious	N	0.503556775	None	None	N
D/W	0.9666	likely_pathogenic	0.9697	pathogenic	-0.3	Destabilizing	0.986	D	0.856	deleterious	None	None	None	None	N
D/Y	0.5426	ambiguous	0.5888	pathogenic	-0.153	Destabilizing	0.981	D	0.805	deleterious	N	0.503810265	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.