TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15448	46567;46568;46569	chr2:178620075;178620074;178620073	chr2:179484802;179484801;179484800
N2AB	13807	41644;41645;41646	chr2:178620075;178620074;178620073	chr2:179484802;179484801;179484800
N2A	12880	38863;38864;38865	chr2:178620075;178620074;178620073	chr2:179484802;179484801;179484800
N2B	6383	19372;19373;19374	chr2:178620075;178620074;178620073	chr2:179484802;179484801;179484800
Novex-1	6508	19747;19748;19749	chr2:178620075;178620074;178620073	chr2:179484802;179484801;179484800
Novex-2	6575	19948;19949;19950	chr2:178620075;178620074;178620073	chr2:179484802;179484801;179484800
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-106
• Domain position: 58
• Structural Position: 139
• Q(SASA): 0.2817
• 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/L	None	None	0.91	N	0.467	0.194	0.596036732933	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
I/A	0.5265	ambiguous	0.6065	pathogenic	-2.687	Highly Destabilizing	0.97	D	0.651	neutral	None	None	None	None	N
I/C	0.7381	likely_pathogenic	0.7752	pathogenic	-1.822	Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	N
I/D	0.8716	likely_pathogenic	0.8982	pathogenic	-2.942	Highly Destabilizing	0.996	D	0.749	deleterious	None	None	None	None	N
I/E	0.6511	likely_pathogenic	0.6947	pathogenic	-2.774	Highly Destabilizing	0.991	D	0.72	prob.delet.	None	None	None	None	N
I/F	0.1871	likely_benign	0.2244	benign	-1.627	Destabilizing	0.998	D	0.6	neutral	N	0.511314617	None	None	N
I/G	0.8491	likely_pathogenic	0.8823	pathogenic	-3.171	Highly Destabilizing	0.996	D	0.715	prob.delet.	None	None	None	None	N
I/H	0.4278	ambiguous	0.4693	ambiguous	-2.518	Highly Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
I/K	0.4569	ambiguous	0.459	ambiguous	-2.267	Highly Destabilizing	0.942	D	0.685	prob.neutral	None	None	None	None	N
I/L	0.1563	likely_benign	0.1831	benign	-1.304	Destabilizing	0.91	D	0.467	neutral	N	0.503201079	None	None	N
I/M	0.1372	likely_benign	0.1606	benign	-1.094	Destabilizing	0.998	D	0.601	neutral	D	0.552922718	None	None	N
I/N	0.363	ambiguous	0.4194	ambiguous	-2.422	Highly Destabilizing	0.994	D	0.749	deleterious	N	0.508426278	None	None	N
I/P	0.9909	likely_pathogenic	0.9905	pathogenic	-1.745	Destabilizing	0.999	D	0.754	deleterious	None	None	None	None	N
I/Q	0.4707	ambiguous	0.5147	ambiguous	-2.389	Highly Destabilizing	0.991	D	0.743	deleterious	None	None	None	None	N
I/R	0.3598	ambiguous	0.3627	ambiguous	-1.755	Destabilizing	0.092	N	0.526	neutral	None	None	None	None	N
I/S	0.4229	ambiguous	0.4934	ambiguous	-3.068	Highly Destabilizing	0.994	D	0.686	prob.neutral	N	0.504722144	None	None	N
I/T	0.22	likely_benign	0.2444	benign	-2.78	Highly Destabilizing	0.98	D	0.621	neutral	N	0.481201794	None	None	N
I/V	0.0897	likely_benign	0.091	benign	-1.745	Destabilizing	0.954	D	0.489	neutral	N	0.446202445	None	None	N
I/W	0.7521	likely_pathogenic	0.7802	pathogenic	-1.99	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
I/Y	0.4794	ambiguous	0.5322	ambiguous	-1.764	Destabilizing	0.999	D	0.695	prob.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.