TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31759	95500;95501;95502	chr2:178545961;178545960;178545959	chr2:179410688;179410687;179410686
N2AB	30118	90577;90578;90579	chr2:178545961;178545960;178545959	chr2:179410688;179410687;179410686
N2A	29191	87796;87797;87798	chr2:178545961;178545960;178545959	chr2:179410688;179410687;179410686
N2B	22694	68305;68306;68307	chr2:178545961;178545960;178545959	chr2:179410688;179410687;179410686
Novex-1	22819	68680;68681;68682	chr2:178545961;178545960;178545959	chr2:179410688;179410687;179410686
Novex-2	22886	68881;68882;68883	chr2:178545961;178545960;178545959	chr2:179410688;179410687;179410686
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-119
• Domain position: 52
• Structural Position: 69
• Q(SASA): 0.2906
• Predicted PPI site: I

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
E/A	rs767475236	-0.527	0.822	N	0.585	0.407	0.329540904979	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	5.58E-05	None	0	None	0	0	0
E/A	rs767475236	-0.527	0.822	N	0.585	0.407	0.329540904979	gnomAD-4.0.0	1.59121E-06	None	None	None	None	I	None	0	0	None	0	2.77331E-05	None	0	0	0	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
E/A	0.1371	likely_benign	0.1446	benign	-0.585	Destabilizing	0.822	D	0.585	neutral	N	0.384647525	None	None	I
E/C	0.784	likely_pathogenic	0.7887	pathogenic	-0.366	Destabilizing	0.998	D	0.751	deleterious	None	None	None	None	I
E/D	0.1627	likely_benign	0.1674	benign	-0.905	Destabilizing	0.006	N	0.171	neutral	N	0.409273824	None	None	I
E/F	0.8568	likely_pathogenic	0.8505	pathogenic	0.197	Stabilizing	0.998	D	0.763	deleterious	None	None	None	None	I
E/G	0.2307	likely_benign	0.2342	benign	-0.96	Destabilizing	0.822	D	0.618	neutral	N	0.454662184	None	None	I
E/H	0.5001	ambiguous	0.5134	ambiguous	0.125	Stabilizing	0.998	D	0.658	neutral	None	None	None	None	I
E/I	0.5838	likely_pathogenic	0.564	pathogenic	0.437	Stabilizing	0.978	D	0.784	deleterious	None	None	None	None	I
E/K	0.2615	likely_benign	0.2636	benign	-0.228	Destabilizing	0.822	D	0.464	neutral	N	0.468090054	None	None	I
E/L	0.5621	ambiguous	0.5549	ambiguous	0.437	Stabilizing	0.978	D	0.773	deleterious	None	None	None	None	I
E/M	0.5848	likely_pathogenic	0.5865	pathogenic	0.679	Stabilizing	0.998	D	0.739	prob.delet.	None	None	None	None	I
E/N	0.322	likely_benign	0.3151	benign	-0.946	Destabilizing	0.915	D	0.628	neutral	None	None	None	None	I
E/P	0.908	likely_pathogenic	0.9201	pathogenic	0.119	Stabilizing	0.978	D	0.761	deleterious	None	None	None	None	I
E/Q	0.1756	likely_benign	0.1805	benign	-0.756	Destabilizing	0.942	D	0.6	neutral	N	0.488465326	None	None	I
E/R	0.3888	ambiguous	0.4031	ambiguous	0.117	Stabilizing	0.978	D	0.665	neutral	None	None	None	None	I
E/S	0.1925	likely_benign	0.1934	benign	-1.185	Destabilizing	0.86	D	0.493	neutral	None	None	None	None	I
E/T	0.2541	likely_benign	0.2542	benign	-0.855	Destabilizing	0.956	D	0.707	prob.neutral	None	None	None	None	I
E/V	0.3126	likely_benign	0.311	benign	0.119	Stabilizing	0.971	D	0.738	prob.delet.	N	0.439692731	None	None	I
E/W	0.9492	likely_pathogenic	0.9542	pathogenic	0.503	Stabilizing	0.998	D	0.754	deleterious	None	None	None	None	I
E/Y	0.7542	likely_pathogenic	0.7462	pathogenic	0.481	Stabilizing	0.998	D	0.75	deleterious	None	None	None	None	I

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.