TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19316	58171;58172;58173	chr2:178594548;178594547;178594546	chr2:179459275;179459274;179459273
N2AB	17675	53248;53249;53250	chr2:178594548;178594547;178594546	chr2:179459275;179459274;179459273
N2A	16748	50467;50468;50469	chr2:178594548;178594547;178594546	chr2:179459275;179459274;179459273
N2B	10251	30976;30977;30978	chr2:178594548;178594547;178594546	chr2:179459275;179459274;179459273
Novex-1	10376	31351;31352;31353	chr2:178594548;178594547;178594546	chr2:179459275;179459274;179459273
Novex-2	10443	31552;31553;31554	chr2:178594548;178594547;178594546	chr2:179459275;179459274;179459273
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: Fn3-28
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.16
• 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/V	rs756090879	-1.564	0.333	N	0.292	0.114	0.559847471112	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
I/V	rs756090879	-1.564	0.333	N	0.292	0.114	0.559847471112	gnomAD-4.0.0	1.59234E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43365E-05	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	0.984	likely_pathogenic	0.9823	pathogenic	-2.522	Highly Destabilizing	0.992	D	0.691	prob.neutral	None	None	None	None	I
I/C	0.979	likely_pathogenic	0.982	pathogenic	-1.622	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
I/D	0.9969	likely_pathogenic	0.9959	pathogenic	-2.99	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
I/E	0.994	likely_pathogenic	0.9934	pathogenic	-2.818	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
I/F	0.9553	likely_pathogenic	0.9487	pathogenic	-1.615	Destabilizing	0.998	D	0.759	deleterious	D	0.5403369	None	None	I
I/G	0.9958	likely_pathogenic	0.9952	pathogenic	-3.0	Highly Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	I
I/H	0.9955	likely_pathogenic	0.9955	pathogenic	-2.467	Highly Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	I
I/K	0.9907	likely_pathogenic	0.99	pathogenic	-1.979	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	I
I/L	0.4287	ambiguous	0.4673	ambiguous	-1.155	Destabilizing	0.889	D	0.506	neutral	D	0.528240009	None	None	I
I/M	0.5757	likely_pathogenic	0.5483	ambiguous	-0.923	Destabilizing	0.998	D	0.72	prob.delet.	D	0.53151549	None	None	I
I/N	0.8717	likely_pathogenic	0.8461	pathogenic	-2.204	Highly Destabilizing	0.999	D	0.841	deleterious	D	0.543885753	None	None	I
I/P	0.9793	likely_pathogenic	0.9758	pathogenic	-1.591	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	I
I/Q	0.9932	likely_pathogenic	0.9931	pathogenic	-2.168	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
I/R	0.9896	likely_pathogenic	0.9897	pathogenic	-1.516	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
I/S	0.9835	likely_pathogenic	0.9796	pathogenic	-2.807	Highly Destabilizing	0.998	D	0.782	deleterious	D	0.543125285	None	None	I
I/T	0.965	likely_pathogenic	0.958	pathogenic	-2.515	Highly Destabilizing	0.989	D	0.806	deleterious	N	0.513664724	None	None	I
I/V	0.1953	likely_benign	0.1788	benign	-1.591	Destabilizing	0.333	N	0.292	neutral	N	0.45895607	None	None	I
I/W	0.9977	likely_pathogenic	0.9979	pathogenic	-2.049	Highly Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	I
I/Y	0.9894	likely_pathogenic	0.989	pathogenic	-1.767	Destabilizing	1.0	D	0.779	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.