TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9199	27820;27821;27822	chr2:178712327;178712326;178712325	chr2:179577054;179577053;179577052
N2AB	8882	26869;26870;26871	chr2:178712327;178712326;178712325	chr2:179577054;179577053;179577052
N2A	7955	24088;24089;24090	chr2:178712327;178712326;178712325	chr2:179577054;179577053;179577052
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: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-77
• Domain position: 88
• Structural Position: 174
• Q(SASA): 0.1047
• 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/K	rs1207087892	None	0.966	N	0.831	0.499	0.650812743361	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
I/K	rs1207087892	None	0.966	N	0.831	0.499	0.650812743361	gnomAD-4.0.0	3.84476E-06	None	None	None	None	N	None	5.07511E-05	0	None	0	0	None	0	0	0	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
I/A	0.7669	likely_pathogenic	0.7681	pathogenic	-2.536	Highly Destabilizing	0.525	D	0.691	prob.neutral	None	None	None	None	N
I/C	0.8575	likely_pathogenic	0.8484	pathogenic	-1.949	Destabilizing	0.998	D	0.775	deleterious	None	None	None	None	N
I/D	0.9887	likely_pathogenic	0.9843	pathogenic	-2.785	Highly Destabilizing	0.991	D	0.838	deleterious	None	None	None	None	N
I/E	0.9809	likely_pathogenic	0.9753	pathogenic	-2.548	Highly Destabilizing	0.974	D	0.827	deleterious	None	None	None	None	N
I/F	0.3267	likely_benign	0.2642	benign	-1.524	Destabilizing	0.949	D	0.757	deleterious	None	None	None	None	N
I/G	0.9451	likely_pathogenic	0.9349	pathogenic	-3.106	Highly Destabilizing	0.974	D	0.83	deleterious	None	None	None	None	N
I/H	0.9585	likely_pathogenic	0.9416	pathogenic	-2.596	Highly Destabilizing	0.998	D	0.822	deleterious	None	None	None	None	N
I/K	0.9682	likely_pathogenic	0.9562	pathogenic	-1.974	Destabilizing	0.966	D	0.831	deleterious	N	0.468849299	None	None	N
I/L	0.1435	likely_benign	0.1343	benign	-0.889	Destabilizing	0.005	N	0.253	neutral	N	0.355275396	None	None	N
I/M	0.1893	likely_benign	0.1768	benign	-0.913	Destabilizing	0.934	D	0.701	prob.neutral	N	0.456567941	None	None	N
I/N	0.8591	likely_pathogenic	0.8268	pathogenic	-2.336	Highly Destabilizing	0.991	D	0.839	deleterious	None	None	None	None	N
I/P	0.9807	likely_pathogenic	0.97	pathogenic	-1.418	Destabilizing	0.991	D	0.841	deleterious	None	None	None	None	N
I/Q	0.9628	likely_pathogenic	0.9512	pathogenic	-2.172	Highly Destabilizing	0.991	D	0.833	deleterious	None	None	None	None	N
I/R	0.9521	likely_pathogenic	0.9333	pathogenic	-1.73	Destabilizing	0.966	D	0.842	deleterious	N	0.480205605	None	None	N
I/S	0.846	likely_pathogenic	0.8291	pathogenic	-3.067	Highly Destabilizing	0.974	D	0.815	deleterious	None	None	None	None	N
I/T	0.7747	likely_pathogenic	0.7676	pathogenic	-2.673	Highly Destabilizing	0.801	D	0.73	prob.delet.	N	0.480205605	None	None	N
I/V	0.0911	likely_benign	0.0923	benign	-1.418	Destabilizing	0.002	N	0.246	neutral	N	0.3661224	None	None	N
I/W	0.9678	likely_pathogenic	0.9497	pathogenic	-1.921	Destabilizing	0.998	D	0.828	deleterious	None	None	None	None	N
I/Y	0.8231	likely_pathogenic	0.7741	pathogenic	-1.621	Destabilizing	0.974	D	0.803	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.