TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4961	15106;15107;15108	chr2:178735565;178735564;178735563	chr2:179600292;179600291;179600290
N2AB	4644	14155;14156;14157	chr2:178735565;178735564;178735563	chr2:179600292;179600291;179600290
N2A	3717	11374;11375;11376	chr2:178735565;178735564;178735563	chr2:179600292;179600291;179600290
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-32
• Domain position: 74
• Structural Position: 157
• Q(SASA): 0.3144
• Predicted PPI site: N

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/I	rs1298192031	-0.232	0.998	N	0.743	0.3	0.373537453441	gnomAD-2.1.1	4.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.95E-06	0
T/I	rs1298192031	-0.232	0.998	N	0.743	0.3	0.373537453441	gnomAD-4.0.0	1.59675E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86285E-06	0	0
T/R	None	None	0.999	N	0.814	0.381	0.397838977388	gnomAD-4.0.0	1.59675E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86285E-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
T/A	0.0874	likely_benign	0.0926	benign	-1.014	Destabilizing	0.996	D	0.593	neutral	D	0.610088984	None	None	N
T/C	0.3664	ambiguous	0.4115	ambiguous	-0.877	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
T/D	0.4098	ambiguous	0.4594	ambiguous	-0.932	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
T/E	0.2547	likely_benign	0.2822	benign	-0.905	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
T/F	0.1444	likely_benign	0.1541	benign	-1.315	Destabilizing	0.999	D	0.831	deleterious	None	None	None	None	N
T/G	0.2834	likely_benign	0.3153	benign	-1.242	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
T/H	0.1887	likely_benign	0.2015	benign	-1.565	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
T/I	0.0945	likely_benign	0.0997	benign	-0.487	Destabilizing	0.998	D	0.743	deleterious	N	0.498825173	None	None	N
T/K	0.1641	likely_benign	0.1751	benign	-0.603	Destabilizing	0.999	D	0.748	deleterious	N	0.394537178	None	None	N
T/L	0.0764	likely_benign	0.0793	benign	-0.487	Destabilizing	0.994	D	0.671	neutral	None	None	None	None	N
T/M	0.0742	likely_benign	0.0748	benign	-0.107	Destabilizing	0.985	D	0.563	neutral	None	None	None	None	N
T/N	0.1322	likely_benign	0.1447	benign	-0.749	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
T/P	0.5694	likely_pathogenic	0.6218	pathogenic	-0.634	Destabilizing	1.0	D	0.813	deleterious	D	0.676178714	None	None	N
T/Q	0.1859	likely_benign	0.1954	benign	-1.019	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
T/R	0.1251	likely_benign	0.1311	benign	-0.373	Destabilizing	0.999	D	0.814	deleterious	N	0.471535028	None	None	N
T/S	0.109	likely_benign	0.1159	benign	-1.004	Destabilizing	0.998	D	0.582	neutral	N	0.512486055	None	None	N
T/V	0.0953	likely_benign	0.1011	benign	-0.634	Destabilizing	0.994	D	0.587	neutral	None	None	None	None	N
T/W	0.4443	ambiguous	0.4767	ambiguous	-1.241	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
T/Y	0.2105	likely_benign	0.2238	benign	-0.933	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N

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.