TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20341	61246;61247;61248	chr2:178590704;178590703;178590702	chr2:179455431;179455430;179455429
N2AB	18700	56323;56324;56325	chr2:178590704;178590703;178590702	chr2:179455431;179455430;179455429
N2A	17773	53542;53543;53544	chr2:178590704;178590703;178590702	chr2:179455431;179455430;179455429
N2B	11276	34051;34052;34053	chr2:178590704;178590703;178590702	chr2:179455431;179455430;179455429
Novex-1	11401	34426;34427;34428	chr2:178590704;178590703;178590702	chr2:179455431;179455430;179455429
Novex-2	11468	34627;34628;34629	chr2:178590704;178590703;178590702	chr2:179455431;179455430;179455429
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-35
• Domain position: 71
• Structural Position: 104
• Q(SASA): 0.1027
• 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
Y/C	rs2050021727	None	1.0	D	0.839	0.882	0.923434868122	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
Y/C	rs2050021727	None	1.0	D	0.839	0.882	0.923434868122	gnomAD-4.0.0	6.57523E-06	None	None	None	None	N	None	0	6.5548E-05	None	0	0	None	0	0	0	0	0
Y/F	None	None	0.999	D	0.751	0.834	0.807677208685	gnomAD-4.0.0	3.18575E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72243E-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
Y/A	0.9895	likely_pathogenic	0.9878	pathogenic	-3.111	Highly Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
Y/C	0.8098	likely_pathogenic	0.8101	pathogenic	-1.793	Destabilizing	1.0	D	0.839	deleterious	D	0.659702509	None	None	N
Y/D	0.9935	likely_pathogenic	0.9892	pathogenic	-3.219	Highly Destabilizing	1.0	D	0.848	deleterious	D	0.685008456	None	None	N
Y/E	0.9978	likely_pathogenic	0.9969	pathogenic	-3.034	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
Y/F	0.2849	likely_benign	0.3152	benign	-1.061	Destabilizing	0.999	D	0.751	deleterious	D	0.627704866	None	None	N
Y/G	0.9847	likely_pathogenic	0.9804	pathogenic	-3.515	Highly Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
Y/H	0.9517	likely_pathogenic	0.9483	pathogenic	-1.936	Destabilizing	1.0	D	0.822	deleterious	D	0.659702509	None	None	N
Y/I	0.9547	likely_pathogenic	0.9554	pathogenic	-1.782	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
Y/K	0.9981	likely_pathogenic	0.9973	pathogenic	-2.178	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
Y/L	0.9273	likely_pathogenic	0.9271	pathogenic	-1.782	Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
Y/M	0.9732	likely_pathogenic	0.9738	pathogenic	-1.508	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
Y/N	0.9643	likely_pathogenic	0.9545	pathogenic	-2.869	Highly Destabilizing	1.0	D	0.848	deleterious	D	0.668787291	None	None	N
Y/P	0.9982	likely_pathogenic	0.9976	pathogenic	-2.238	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
Y/Q	0.996	likely_pathogenic	0.9952	pathogenic	-2.679	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
Y/R	0.991	likely_pathogenic	0.9886	pathogenic	-1.812	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
Y/S	0.9601	likely_pathogenic	0.9525	pathogenic	-3.255	Highly Destabilizing	1.0	D	0.859	deleterious	D	0.685008456	None	None	N
Y/T	0.9858	likely_pathogenic	0.9839	pathogenic	-2.96	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
Y/V	0.8819	likely_pathogenic	0.8838	pathogenic	-2.238	Highly Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
Y/W	0.6945	likely_pathogenic	0.7071	pathogenic	-0.38	Destabilizing	1.0	D	0.798	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.