TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17601	53026;53027;53028	chr2:178607986;178607985;178607984	chr2:179472713;179472712;179472711
N2AB	15960	48103;48104;48105	chr2:178607986;178607985;178607984	chr2:179472713;179472712;179472711
N2A	15033	45322;45323;45324	chr2:178607986;178607985;178607984	chr2:179472713;179472712;179472711
N2B	8536	25831;25832;25833	chr2:178607986;178607985;178607984	chr2:179472713;179472712;179472711
Novex-1	8661	26206;26207;26208	chr2:178607986;178607985;178607984	chr2:179472713;179472712;179472711
Novex-2	8728	26407;26408;26409	chr2:178607986;178607985;178607984	chr2:179472713;179472712;179472711
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-16
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.1875
• 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
I/T	rs774032287	-2.06	0.978	N	0.762	0.511	None	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	2.67E-05	0
I/T	rs774032287	-2.06	0.978	N	0.762	0.511	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/T	rs774032287	-2.06	0.978	N	0.762	0.511	None	gnomAD-4.0.0	6.82059E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.32731E-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
I/A	0.9095	likely_pathogenic	0.8828	pathogenic	-1.97	Destabilizing	0.983	D	0.655	neutral	None	None	None	None	I
I/C	0.9711	likely_pathogenic	0.9696	pathogenic	-1.146	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
I/D	0.9941	likely_pathogenic	0.9929	pathogenic	-1.462	Destabilizing	0.999	D	0.827	deleterious	None	None	None	None	I
I/E	0.9846	likely_pathogenic	0.9835	pathogenic	-1.413	Destabilizing	0.999	D	0.819	deleterious	None	None	None	None	I
I/F	0.8597	likely_pathogenic	0.8156	pathogenic	-1.303	Destabilizing	0.997	D	0.724	prob.delet.	D	0.522068061	None	None	I
I/G	0.9884	likely_pathogenic	0.9858	pathogenic	-2.35	Highly Destabilizing	0.999	D	0.817	deleterious	None	None	None	None	I
I/H	0.9922	likely_pathogenic	0.9907	pathogenic	-1.504	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	I
I/K	0.9786	likely_pathogenic	0.978	pathogenic	-1.435	Destabilizing	0.999	D	0.818	deleterious	None	None	None	None	I
I/L	0.4035	ambiguous	0.4067	ambiguous	-0.966	Destabilizing	0.798	D	0.4	neutral	D	0.528509368	None	None	I
I/M	0.4426	ambiguous	0.402	ambiguous	-0.707	Destabilizing	0.997	D	0.686	prob.neutral	D	0.524602956	None	None	I
I/N	0.9218	likely_pathogenic	0.9108	pathogenic	-1.298	Destabilizing	0.999	D	0.825	deleterious	D	0.525616914	None	None	I
I/P	0.924	likely_pathogenic	0.9245	pathogenic	-1.271	Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	I
I/Q	0.9836	likely_pathogenic	0.983	pathogenic	-1.423	Destabilizing	0.999	D	0.819	deleterious	None	None	None	None	I
I/R	0.9729	likely_pathogenic	0.9721	pathogenic	-0.83	Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	I
I/S	0.9529	likely_pathogenic	0.943	pathogenic	-1.952	Destabilizing	0.997	D	0.796	deleterious	D	0.536377335	None	None	I
I/T	0.7945	likely_pathogenic	0.7534	pathogenic	-1.778	Destabilizing	0.978	D	0.762	deleterious	N	0.51350014	None	None	I
I/V	0.1353	likely_benign	0.1175	benign	-1.271	Destabilizing	0.198	N	0.223	neutral	N	0.490201696	None	None	I
I/W	0.9941	likely_pathogenic	0.9923	pathogenic	-1.416	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
I/Y	0.975	likely_pathogenic	0.9687	pathogenic	-1.208	Destabilizing	0.999	D	0.775	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.