TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25633	77122;77123;77124	chr2:178569235;178569234;178569233	chr2:179433962;179433961;179433960
N2AB	23992	72199;72200;72201	chr2:178569235;178569234;178569233	chr2:179433962;179433961;179433960
N2A	23065	69418;69419;69420	chr2:178569235;178569234;178569233	chr2:179433962;179433961;179433960
N2B	16568	49927;49928;49929	chr2:178569235;178569234;178569233	chr2:179433962;179433961;179433960
Novex-1	16693	50302;50303;50304	chr2:178569235;178569234;178569233	chr2:179433962;179433961;179433960
Novex-2	16760	50503;50504;50505	chr2:178569235;178569234;178569233	chr2:179433962;179433961;179433960
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: Fn3-74
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.204
• Predicted PPI site: I

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/V	None	None	0.05	N	0.253	0.117	0.523650220922	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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	0.9762	likely_pathogenic	0.9816	pathogenic	-2.511	Highly Destabilizing	0.997	D	0.677	prob.neutral	None	None	None	None	I
I/C	0.9711	likely_pathogenic	0.976	pathogenic	-1.478	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
I/D	0.9984	likely_pathogenic	0.9988	pathogenic	-2.572	Highly Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	I
I/E	0.994	likely_pathogenic	0.9951	pathogenic	-2.471	Highly Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	I
I/F	0.9089	likely_pathogenic	0.9237	pathogenic	-1.718	Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	I
I/G	0.9943	likely_pathogenic	0.9957	pathogenic	-2.947	Highly Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
I/H	0.9958	likely_pathogenic	0.9967	pathogenic	-2.279	Highly Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	I
I/K	0.9903	likely_pathogenic	0.9913	pathogenic	-1.906	Destabilizing	0.993	D	0.828	deleterious	D	0.544708674	None	None	I
I/L	0.4258	ambiguous	0.4703	ambiguous	-1.298	Destabilizing	0.388	N	0.443	neutral	N	0.486504661	None	None	I
I/M	0.4961	ambiguous	0.551	ambiguous	-0.882	Destabilizing	0.995	D	0.711	prob.delet.	D	0.543694716	None	None	I
I/N	0.948	likely_pathogenic	0.9601	pathogenic	-1.882	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
I/P	0.9682	likely_pathogenic	0.9732	pathogenic	-1.679	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
I/Q	0.9904	likely_pathogenic	0.9923	pathogenic	-1.961	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
I/R	0.9875	likely_pathogenic	0.9895	pathogenic	-1.321	Destabilizing	1.0	D	0.831	deleterious	D	0.556229563	None	None	I
I/S	0.9774	likely_pathogenic	0.9825	pathogenic	-2.505	Highly Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
I/T	0.9437	likely_pathogenic	0.9536	pathogenic	-2.286	Highly Destabilizing	0.986	D	0.787	deleterious	D	0.523375188	None	None	I
I/V	0.1186	likely_benign	0.1197	benign	-1.679	Destabilizing	0.05	N	0.253	neutral	N	0.460841581	None	None	I
I/W	0.997	likely_pathogenic	0.9976	pathogenic	-1.997	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
I/Y	0.9862	likely_pathogenic	0.9883	pathogenic	-1.784	Destabilizing	0.997	D	0.783	deleterious	None	None	None	None	I

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.