TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5115	15568;15569;15570	chr2:178734481;178734480;178734479	chr2:179599208;179599207;179599206
N2AB	4798	14617;14618;14619	chr2:178734481;178734480;178734479	chr2:179599208;179599207;179599206
N2A	3871	11836;11837;11838	chr2:178734481;178734480;178734479	chr2:179599208;179599207;179599206
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-34
• Domain position: 41
• Structural Position: 58
• Q(SASA): 0.1213
• 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
I/T	rs1436728714	-2.222	0.978	D	0.629	0.547	0.780223249243	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
I/T	rs1436728714	-2.222	0.978	D	0.629	0.547	0.780223249243	gnomAD-4.0.0	1.59148E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43332E-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	0.9553	likely_pathogenic	0.9701	pathogenic	-2.053	Highly Destabilizing	0.983	D	0.537	neutral	None	None	None	None	N
I/C	0.9599	likely_pathogenic	0.9796	pathogenic	-1.135	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
I/D	0.9989	likely_pathogenic	0.9993	pathogenic	-2.572	Highly Destabilizing	0.999	D	0.807	deleterious	None	None	None	None	N
I/E	0.9946	likely_pathogenic	0.9962	pathogenic	-2.312	Highly Destabilizing	0.999	D	0.796	deleterious	None	None	None	None	N
I/F	0.5438	ambiguous	0.6662	pathogenic	-1.288	Destabilizing	0.997	D	0.639	neutral	D	0.64739827	None	None	N
I/G	0.9917	likely_pathogenic	0.9948	pathogenic	-2.579	Highly Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	N
I/H	0.9881	likely_pathogenic	0.9932	pathogenic	-2.13	Highly Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
I/K	0.9865	likely_pathogenic	0.991	pathogenic	-1.498	Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
I/L	0.1694	likely_benign	0.205	benign	-0.518	Destabilizing	0.798	D	0.393	neutral	N	0.46440445	None	None	N
I/M	0.2349	likely_benign	0.2961	benign	-0.434	Destabilizing	0.997	D	0.652	neutral	D	0.593011275	None	None	N
I/N	0.9761	likely_pathogenic	0.984	pathogenic	-1.997	Destabilizing	0.999	D	0.814	deleterious	D	0.724769076	None	None	N
I/P	0.993	likely_pathogenic	0.9943	pathogenic	-1.014	Destabilizing	0.999	D	0.811	deleterious	None	None	None	None	N
I/Q	0.9817	likely_pathogenic	0.988	pathogenic	-1.786	Destabilizing	0.999	D	0.808	deleterious	None	None	None	None	N
I/R	0.9801	likely_pathogenic	0.9863	pathogenic	-1.436	Destabilizing	0.999	D	0.812	deleterious	None	None	None	None	N
I/S	0.9777	likely_pathogenic	0.985	pathogenic	-2.588	Highly Destabilizing	0.997	D	0.715	prob.delet.	D	0.663736184	None	None	N
I/T	0.9634	likely_pathogenic	0.9747	pathogenic	-2.177	Highly Destabilizing	0.978	D	0.629	neutral	D	0.668518718	None	None	N
I/V	0.155	likely_benign	0.1801	benign	-1.014	Destabilizing	0.198	N	0.211	neutral	N	0.502320989	None	None	N
I/W	0.9791	likely_pathogenic	0.9887	pathogenic	-1.7	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
I/Y	0.9425	likely_pathogenic	0.9649	pathogenic	-1.315	Destabilizing	0.999	D	0.713	prob.delet.	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.