TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21749	65470;65471;65472	chr2:178584306;178584305;178584304	chr2:179449033;179449032;179449031
N2AB	20108	60547;60548;60549	chr2:178584306;178584305;178584304	chr2:179449033;179449032;179449031
N2A	19181	57766;57767;57768	chr2:178584306;178584305;178584304	chr2:179449033;179449032;179449031
N2B	12684	38275;38276;38277	chr2:178584306;178584305;178584304	chr2:179449033;179449032;179449031
Novex-1	12809	38650;38651;38652	chr2:178584306;178584305;178584304	chr2:179449033;179449032;179449031
Novex-2	12876	38851;38852;38853	chr2:178584306;178584305;178584304	chr2:179449033;179449032;179449031
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-45
• Domain position: 91
• Structural Position: 124
• Q(SASA): 0.2771
• 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
T/I	rs557155501	None	0.999	N	0.865	0.34	0.501685917333	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/I	rs557155501	None	0.999	N	0.865	0.34	0.501685917333	gnomAD-4.0.0	3.14023E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.28636E-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
T/A	0.3411	ambiguous	0.2706	benign	-1.047	Destabilizing	0.997	D	0.649	prob.neutral	N	0.515763784	None	None	N
T/C	0.7427	likely_pathogenic	0.6743	pathogenic	-0.49	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
T/D	0.9746	likely_pathogenic	0.9549	pathogenic	-0.411	Destabilizing	0.999	D	0.857	deleterious	None	None	None	None	N
T/E	0.9701	likely_pathogenic	0.9552	pathogenic	-0.265	Destabilizing	0.999	D	0.855	deleterious	None	None	None	None	N
T/F	0.9707	likely_pathogenic	0.9529	pathogenic	-0.765	Destabilizing	0.999	D	0.885	deleterious	None	None	None	None	N
T/G	0.6727	likely_pathogenic	0.5797	pathogenic	-1.433	Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	N
T/H	0.9688	likely_pathogenic	0.951	pathogenic	-1.502	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
T/I	0.8908	likely_pathogenic	0.8542	pathogenic	-0.055	Destabilizing	0.999	D	0.865	deleterious	N	0.505738791	None	None	N
T/K	0.9776	likely_pathogenic	0.963	pathogenic	-0.332	Destabilizing	0.999	D	0.857	deleterious	N	0.461628186	None	None	N
T/L	0.5873	likely_pathogenic	0.5362	ambiguous	-0.055	Destabilizing	0.998	D	0.785	deleterious	None	None	None	None	N
T/M	0.4396	ambiguous	0.3887	ambiguous	0.003	Stabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
T/N	0.8256	likely_pathogenic	0.7488	pathogenic	-0.719	Destabilizing	0.999	D	0.79	deleterious	None	None	None	None	N
T/P	0.8835	likely_pathogenic	0.8563	pathogenic	-0.353	Destabilizing	0.999	D	0.839	deleterious	N	0.485354755	None	None	N
T/Q	0.9437	likely_pathogenic	0.9153	pathogenic	-0.594	Destabilizing	0.999	D	0.83	deleterious	None	None	None	None	N
T/R	0.9664	likely_pathogenic	0.9467	pathogenic	-0.465	Destabilizing	0.999	D	0.847	deleterious	N	0.484340797	None	None	N
T/S	0.2992	likely_benign	0.2279	benign	-1.079	Destabilizing	0.997	D	0.646	neutral	N	0.349588015	None	None	N
T/V	0.6546	likely_pathogenic	0.5948	pathogenic	-0.353	Destabilizing	0.998	D	0.714	prob.delet.	None	None	None	None	N
T/W	0.9948	likely_pathogenic	0.9907	pathogenic	-0.782	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
T/Y	0.9861	likely_pathogenic	0.977	pathogenic	-0.459	Destabilizing	1.0	D	0.897	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.