TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30062	90409;90410;90411	chr2:178552716;178552715;178552714	chr2:179417443;179417442;179417441
N2AB	28421	85486;85487;85488	chr2:178552716;178552715;178552714	chr2:179417443;179417442;179417441
N2A	27494	82705;82706;82707	chr2:178552716;178552715;178552714	chr2:179417443;179417442;179417441
N2B	20997	63214;63215;63216	chr2:178552716;178552715;178552714	chr2:179417443;179417442;179417441
Novex-1	21122	63589;63590;63591	chr2:178552716;178552715;178552714	chr2:179417443;179417442;179417441
Novex-2	21189	63790;63791;63792	chr2:178552716;178552715;178552714	chr2:179417443;179417442;179417441
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-107
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.1705
• 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/F	rs931535269	-1.72	0.991	D	0.755	0.428	0.704837425536	gnomAD-2.1.1	1.07E-05	None	None	None	None	I	None	1.23957E-04	0	None	0	0	None	0	None	0	0	0
I/F	rs931535269	-1.72	0.991	D	0.755	0.428	0.704837425536	gnomAD-3.1.2	5.91E-05	None	None	None	None	I	None	1.92911E-04	0	0	0	0	None	0	0	0	0	4.78011E-04
I/F	rs931535269	-1.72	0.991	D	0.755	0.428	0.704837425536	gnomAD-4.0.0	1.28084E-05	None	None	None	None	I	None	1.5213E-04	0	None	0	0	None	0	0	0	0	2.84398E-05
I/T	rs773537655	-2.379	0.939	N	0.755	0.482	0.779659085684	gnomAD-2.1.1	7.13E-06	None	None	None	None	I	None	8.27E-05	0	None	0	0	None	0	None	0	0	0
I/T	rs773537655	-2.379	0.939	N	0.755	0.482	0.779659085684	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	4.82E-05	0	0	0	0	None	0	0	0	0	0
I/T	rs773537655	-2.379	0.939	N	0.755	0.482	0.779659085684	gnomAD-4.0.0	3.09824E-06	None	None	None	None	I	None	4.00384E-05	0	None	0	0	None	0	0	1.69515E-06	0	0
I/V	rs931535269	None	0.02	N	0.261	0.169	0.480198768302	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	6.54E-05	0	0	0	None	0	0	0	0	0
I/V	rs931535269	None	0.02	N	0.261	0.169	0.480198768302	gnomAD-4.0.0	6.56944E-06	None	None	None	None	I	None	0	6.54365E-05	None	0	0	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
I/A	0.9416	likely_pathogenic	0.917	pathogenic	-2.344	Highly Destabilizing	0.91	D	0.628	neutral	None	None	None	None	I
I/C	0.9625	likely_pathogenic	0.9446	pathogenic	-1.529	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	I
I/D	0.9946	likely_pathogenic	0.9908	pathogenic	-2.103	Highly Destabilizing	0.998	D	0.793	deleterious	None	None	None	None	I
I/E	0.9877	likely_pathogenic	0.9805	pathogenic	-1.996	Destabilizing	0.993	D	0.78	deleterious	None	None	None	None	I
I/F	0.8459	likely_pathogenic	0.7851	pathogenic	-1.534	Destabilizing	0.991	D	0.755	deleterious	D	0.541818157	None	None	I
I/G	0.9889	likely_pathogenic	0.9823	pathogenic	-2.796	Highly Destabilizing	0.993	D	0.786	deleterious	None	None	None	None	I
I/H	0.986	likely_pathogenic	0.9757	pathogenic	-2.057	Highly Destabilizing	0.999	D	0.754	deleterious	None	None	None	None	I
I/K	0.9764	likely_pathogenic	0.9637	pathogenic	-1.702	Destabilizing	0.993	D	0.779	deleterious	None	None	None	None	I
I/L	0.3384	likely_benign	0.2994	benign	-1.101	Destabilizing	0.58	D	0.464	neutral	N	0.48765675	None	None	I
I/M	0.4318	ambiguous	0.3693	ambiguous	-0.864	Destabilizing	0.991	D	0.711	prob.delet.	D	0.544353052	None	None	I
I/N	0.7971	likely_pathogenic	0.7294	pathogenic	-1.686	Destabilizing	0.997	D	0.793	deleterious	D	0.522489815	None	None	I
I/P	0.9475	likely_pathogenic	0.9343	pathogenic	-1.489	Destabilizing	0.998	D	0.791	deleterious	None	None	None	None	I
I/Q	0.9762	likely_pathogenic	0.9614	pathogenic	-1.748	Destabilizing	0.998	D	0.789	deleterious	None	None	None	None	I
I/R	0.9698	likely_pathogenic	0.9522	pathogenic	-1.178	Destabilizing	0.998	D	0.795	deleterious	None	None	None	None	I
I/S	0.9353	likely_pathogenic	0.9049	pathogenic	-2.396	Highly Destabilizing	0.991	D	0.753	deleterious	D	0.544606542	None	None	I
I/T	0.8724	likely_pathogenic	0.821	pathogenic	-2.156	Highly Destabilizing	0.939	D	0.755	deleterious	N	0.508398032	None	None	I
I/V	0.1252	likely_benign	0.1148	benign	-1.489	Destabilizing	0.02	N	0.261	neutral	N	0.485891955	None	None	I
I/W	0.9954	likely_pathogenic	0.9921	pathogenic	-1.743	Destabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	I
I/Y	0.9777	likely_pathogenic	0.9638	pathogenic	-1.516	Destabilizing	0.998	D	0.77	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.