TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32404	97435;97436;97437	chr2:178542546;178542545;178542544	chr2:179407273;179407272;179407271
N2AB	30763	92512;92513;92514	chr2:178542546;178542545;178542544	chr2:179407273;179407272;179407271
N2A	29836	89731;89732;89733	chr2:178542546;178542545;178542544	chr2:179407273;179407272;179407271
N2B	23339	70240;70241;70242	chr2:178542546;178542545;178542544	chr2:179407273;179407272;179407271
Novex-1	23464	70615;70616;70617	chr2:178542546;178542545;178542544	chr2:179407273;179407272;179407271
Novex-2	23531	70816;70817;70818	chr2:178542546;178542545;178542544	chr2:179407273;179407272;179407271
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: Fn3-124
• Domain position: 6
• Structural Position: 6
• Q(SASA): 0.2179
• 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	rs752957686	0.243	None	N	0.295	0.107	0.132336055621	gnomAD-2.1.1	4.08E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.02E-06	0
T/I	rs752957686	0.243	None	N	0.295	0.107	0.132336055621	gnomAD-4.0.0	2.75297E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.61901E-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	0.0713	likely_benign	0.0653	benign	-0.684	Destabilizing	0.012	N	0.413	neutral	N	0.475986313	None	None	N
T/C	0.2347	likely_benign	0.2257	benign	-0.451	Destabilizing	0.824	D	0.585	neutral	None	None	None	None	N
T/D	0.3912	ambiguous	0.3463	ambiguous	-0.361	Destabilizing	0.081	N	0.587	neutral	None	None	None	None	N
T/E	0.2234	likely_benign	0.2007	benign	-0.322	Destabilizing	0.081	N	0.566	neutral	None	None	None	None	N
T/F	0.2302	likely_benign	0.1914	benign	-0.547	Destabilizing	0.38	N	0.681	prob.neutral	None	None	None	None	N
T/G	0.19	likely_benign	0.1777	benign	-0.993	Destabilizing	0.081	N	0.565	neutral	None	None	None	None	N
T/H	0.2159	likely_benign	0.1903	benign	-1.345	Destabilizing	0.824	D	0.658	neutral	None	None	None	None	N
T/I	0.1017	likely_benign	0.0852	benign	0.059	Stabilizing	None	N	0.295	neutral	N	0.468325413	None	None	N
T/K	0.0999	likely_benign	0.0946	benign	-0.874	Destabilizing	0.062	N	0.581	neutral	N	0.45738191	None	None	N
T/L	0.0805	likely_benign	0.0728	benign	0.059	Stabilizing	0.012	N	0.392	neutral	None	None	None	None	N
T/M	0.0854	likely_benign	0.0784	benign	0.172	Stabilizing	0.38	N	0.581	neutral	None	None	None	None	N
T/N	0.1345	likely_benign	0.1193	benign	-0.861	Destabilizing	0.081	N	0.589	neutral	None	None	None	None	N
T/P	0.3911	ambiguous	0.304	benign	-0.155	Destabilizing	0.317	N	0.643	neutral	N	0.455747114	None	None	N
T/Q	0.1553	likely_benign	0.1424	benign	-0.887	Destabilizing	0.38	N	0.612	neutral	None	None	None	None	N
T/R	0.0934	likely_benign	0.0818	benign	-0.796	Destabilizing	0.317	N	0.623	neutral	N	0.495572152	None	None	N
T/S	0.1049	likely_benign	0.0968	benign	-1.075	Destabilizing	None	N	0.263	neutral	N	0.45634176	None	None	N
T/V	0.0787	likely_benign	0.0713	benign	-0.155	Destabilizing	None	N	0.197	neutral	None	None	None	None	N
T/W	0.5974	likely_pathogenic	0.5244	ambiguous	-0.582	Destabilizing	0.935	D	0.683	prob.neutral	None	None	None	None	N
T/Y	0.2857	likely_benign	0.2493	benign	-0.338	Destabilizing	0.555	D	0.669	neutral	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.