TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9426	28501;28502;28503	chr2:178710821;178710820;178710819	chr2:179575548;179575547;179575546
N2AB	9109	27550;27551;27552	chr2:178710821;178710820;178710819	chr2:179575548;179575547;179575546
N2A	8182	24769;24770;24771	chr2:178710821;178710820;178710819	chr2:179575548;179575547;179575546
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-80
• Domain position: 30
• Structural Position: 44
• Q(SASA): 0.1888
• 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/T	None	None	0.994	None	0.619	0.362	0.734446920103	gnomAD-4.0.0	3.4208E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.59769E-06	0	1.65634E-05

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	0.7074	likely_pathogenic	0.8604	pathogenic	-2.415	Highly Destabilizing	0.992	D	0.499	neutral	None	None	None	None	I
I/C	0.9211	likely_pathogenic	0.9666	pathogenic	-1.591	Destabilizing	1.0	D	0.62	neutral	None	None	None	None	I
I/D	0.976	likely_pathogenic	0.9936	pathogenic	-2.514	Highly Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	I
I/E	0.9261	likely_pathogenic	0.9765	pathogenic	-2.395	Highly Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
I/F	0.2511	likely_benign	0.6119	pathogenic	-1.545	Destabilizing	0.998	D	0.591	neutral	None	None	None	None	I
I/G	0.9194	likely_pathogenic	0.9751	pathogenic	-2.867	Highly Destabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	I
I/H	0.9222	likely_pathogenic	0.983	pathogenic	-2.243	Highly Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	I
I/K	0.8612	likely_pathogenic	0.9542	pathogenic	-1.883	Destabilizing	0.998	D	0.732	prob.delet.	None	None	None	None	I
I/L	0.1424	likely_benign	0.2211	benign	-1.159	Destabilizing	0.889	D	0.355	neutral	None	None	None	None	I
I/M	0.1188	likely_benign	0.2088	benign	-0.942	Destabilizing	0.889	D	0.391	neutral	None	None	None	None	I
I/N	0.807	likely_pathogenic	0.9339	pathogenic	-1.913	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
I/P	0.8726	likely_pathogenic	0.9278	pathogenic	-1.554	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	I
I/Q	0.8422	likely_pathogenic	0.9511	pathogenic	-1.955	Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	I
I/R	0.7921	likely_pathogenic	0.9302	pathogenic	-1.374	Destabilizing	0.998	D	0.755	deleterious	None	None	None	None	I
I/S	0.7652	likely_pathogenic	0.9026	pathogenic	-2.556	Highly Destabilizing	0.999	D	0.631	neutral	None	None	None	None	I
I/T	0.7722	likely_pathogenic	0.8903	pathogenic	-2.314	Highly Destabilizing	0.994	D	0.619	neutral	None	None	None	None	I
I/V	0.0981	likely_benign	0.1171	benign	-1.554	Destabilizing	0.889	D	0.41	neutral	None	None	None	None	I
I/W	0.9006	likely_pathogenic	0.9785	pathogenic	-1.84	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
I/Y	0.753	likely_pathogenic	0.9427	pathogenic	-1.603	Destabilizing	1.0	D	0.67	neutral	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.