TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21989	66190;66191;66192	chr2:178582491;178582490;178582489	chr2:179447218;179447217;179447216
N2AB	20348	61267;61268;61269	chr2:178582491;178582490;178582489	chr2:179447218;179447217;179447216
N2A	19421	58486;58487;58488	chr2:178582491;178582490;178582489	chr2:179447218;179447217;179447216
N2B	12924	38995;38996;38997	chr2:178582491;178582490;178582489	chr2:179447218;179447217;179447216
Novex-1	13049	39370;39371;39372	chr2:178582491;178582490;178582489	chr2:179447218;179447217;179447216
Novex-2	13116	39571;39572;39573	chr2:178582491;178582490;178582489	chr2:179447218;179447217;179447216
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-47
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.3512
• 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
T/A	rs1183678109	-0.637	0.958	N	0.443	0.453	0.33835085245	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
T/A	rs1183678109	-0.637	0.958	N	0.443	0.453	0.33835085245	gnomAD-4.0.0	1.59323E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43377E-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
T/A	0.2293	likely_benign	0.2138	benign	-0.642	Destabilizing	0.958	D	0.443	neutral	N	0.503630956	None	None	I
T/C	0.6959	likely_pathogenic	0.6296	pathogenic	-0.362	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	I
T/D	0.7797	likely_pathogenic	0.7473	pathogenic	-0.39	Destabilizing	0.991	D	0.694	prob.neutral	None	None	None	None	I
T/E	0.6105	likely_pathogenic	0.5796	pathogenic	-0.438	Destabilizing	0.938	D	0.599	neutral	None	None	None	None	I
T/F	0.6295	likely_pathogenic	0.5766	pathogenic	-0.93	Destabilizing	0.998	D	0.824	deleterious	None	None	None	None	I
T/G	0.5281	ambiguous	0.4891	ambiguous	-0.838	Destabilizing	0.991	D	0.705	prob.neutral	None	None	None	None	I
T/H	0.5906	likely_pathogenic	0.5456	ambiguous	-1.174	Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	I
T/I	0.4064	ambiguous	0.3418	ambiguous	-0.226	Destabilizing	0.994	D	0.787	deleterious	N	0.515366713	None	None	I
T/K	0.4425	ambiguous	0.4196	ambiguous	-0.661	Destabilizing	0.938	D	0.663	neutral	None	None	None	None	I
T/L	0.2102	likely_benign	0.1865	benign	-0.226	Destabilizing	0.968	D	0.598	neutral	None	None	None	None	I
T/M	0.1635	likely_benign	0.1445	benign	0.209	Stabilizing	0.999	D	0.754	deleterious	None	None	None	None	I
T/N	0.3375	likely_benign	0.3096	benign	-0.508	Destabilizing	0.988	D	0.679	prob.neutral	N	0.497389986	None	None	I
T/P	0.8655	likely_pathogenic	0.8472	pathogenic	-0.335	Destabilizing	0.994	D	0.787	deleterious	D	0.534865943	None	None	I
T/Q	0.4181	ambiguous	0.4068	ambiguous	-0.806	Destabilizing	0.484	N	0.365	neutral	None	None	None	None	I
T/R	0.423	ambiguous	0.3916	ambiguous	-0.308	Destabilizing	0.982	D	0.773	deleterious	None	None	None	None	I
T/S	0.1833	likely_benign	0.1736	benign	-0.729	Destabilizing	0.958	D	0.411	neutral	N	0.503552209	None	None	I
T/V	0.3154	likely_benign	0.2628	benign	-0.335	Destabilizing	0.968	D	0.533	neutral	None	None	None	None	I
T/W	0.8753	likely_pathogenic	0.8578	pathogenic	-0.86	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	I
T/Y	0.7039	likely_pathogenic	0.6607	pathogenic	-0.62	Destabilizing	0.998	D	0.829	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.