TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32685	98278;98279;98280	chr2:178540113;178540112;178540111	chr2:179404840;179404839;179404838
N2AB	31044	93355;93356;93357	chr2:178540113;178540112;178540111	chr2:179404840;179404839;179404838
N2A	30117	90574;90575;90576	chr2:178540113;178540112;178540111	chr2:179404840;179404839;179404838
N2B	23620	71083;71084;71085	chr2:178540113;178540112;178540111	chr2:179404840;179404839;179404838
Novex-1	23745	71458;71459;71460	chr2:178540113;178540112;178540111	chr2:179404840;179404839;179404838
Novex-2	23812	71659;71660;71661	chr2:178540113;178540112;178540111	chr2:179404840;179404839;179404838
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-126
• Domain position: 86
• Structural Position: 119
• Q(SASA): 0.8504
• 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/G	rs762387276	-0.162	1.0	N	0.706	0.533	0.499921029546	gnomAD-2.1.1	2.43E-05	None	None	None	None	I	None	0	0	None	0	2.22643E-04	None	0	None	4.69E-05	8.93E-06	0
E/G	rs762387276	-0.162	1.0	N	0.706	0.533	0.499921029546	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	0	0	0	0	3.85356E-04	None	9.42E-05	0	0	0	0
E/G	rs762387276	-0.162	1.0	N	0.706	0.533	0.499921029546	gnomAD-4.0.0	1.67248E-05	None	None	None	None	I	None	0	0	None	0	1.69903E-04	None	9.4307E-05	0	0	0	0
E/K	None	None	0.999	N	0.69	0.376	0.381071309025	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
E/A	0.1861	likely_benign	0.2069	benign	-0.396	Destabilizing	0.999	D	0.709	prob.delet.	N	0.471697953	None	None	I
E/C	0.7839	likely_pathogenic	0.8081	pathogenic	-0.177	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
E/D	0.1282	likely_benign	0.1313	benign	-0.393	Destabilizing	0.999	D	0.589	neutral	N	0.511035541	None	None	I
E/F	0.653	likely_pathogenic	0.7094	pathogenic	-0.195	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	I
E/G	0.2559	likely_benign	0.3018	benign	-0.603	Destabilizing	1.0	D	0.706	prob.neutral	N	0.493245248	None	None	I
E/H	0.4879	ambiguous	0.5333	ambiguous	0.101	Stabilizing	1.0	D	0.651	neutral	None	None	None	None	I
E/I	0.2547	likely_benign	0.2812	benign	0.119	Stabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	I
E/K	0.1583	likely_benign	0.1957	benign	0.205	Stabilizing	0.999	D	0.69	prob.neutral	N	0.516980079	None	None	I
E/L	0.3101	likely_benign	0.3433	ambiguous	0.119	Stabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	I
E/M	0.3682	ambiguous	0.4105	ambiguous	0.144	Stabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
E/N	0.2752	likely_benign	0.2947	benign	-0.139	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
E/P	0.3602	ambiguous	0.3936	ambiguous	-0.032	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
E/Q	0.1515	likely_benign	0.1685	benign	-0.095	Destabilizing	1.0	D	0.69	prob.neutral	N	0.473268115	None	None	I
E/R	0.2895	likely_benign	0.3442	ambiguous	0.489	Stabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
E/S	0.2434	likely_benign	0.2576	benign	-0.311	Destabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	I
E/T	0.2491	likely_benign	0.2713	benign	-0.141	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
E/V	0.1782	likely_benign	0.1981	benign	-0.032	Destabilizing	1.0	D	0.75	deleterious	N	0.486385621	None	None	I
E/W	0.8665	likely_pathogenic	0.9071	pathogenic	-0.023	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
E/Y	0.5429	ambiguous	0.6052	pathogenic	0.051	Stabilizing	1.0	D	0.734	prob.delet.	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.