TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16844	50755;50756;50757	chr2:178611779;178611778;178611777	chr2:179476506;179476505;179476504
N2AB	15203	45832;45833;45834	chr2:178611779;178611778;178611777	chr2:179476506;179476505;179476504
N2A	14276	43051;43052;43053	chr2:178611779;178611778;178611777	chr2:179476506;179476505;179476504
N2B	7779	23560;23561;23562	chr2:178611779;178611778;178611777	chr2:179476506;179476505;179476504
Novex-1	7904	23935;23936;23937	chr2:178611779;178611778;178611777	chr2:179476506;179476505;179476504
Novex-2	7971	24136;24137;24138	chr2:178611779;178611778;178611777	chr2:179476506;179476505;179476504
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-10
• Domain position: 94
• Structural Position: 127
• Q(SASA): 0.2131
• 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
L/P	rs764983586	-1.074	0.994	N	0.846	0.314	0.790474174173	gnomAD-2.1.1	2.83E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.25E-05	0
L/P	rs764983586	-1.074	0.994	N	0.846	0.314	0.790474174173	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	4.42E-05	0	0
L/P	rs764983586	-1.074	0.994	N	0.846	0.314	0.790474174173	gnomAD-4.0.0	1.73669E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.20508E-05	0	3.20585E-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
L/A	0.5464	ambiguous	0.5774	pathogenic	-2.022	Highly Destabilizing	0.825	D	0.618	neutral	None	None	None	None	N
L/C	0.5605	ambiguous	0.5315	ambiguous	-1.477	Destabilizing	0.999	D	0.701	prob.delet.	None	None	None	None	N
L/D	0.9659	likely_pathogenic	0.9638	pathogenic	-1.452	Destabilizing	0.995	D	0.842	deleterious	None	None	None	None	N
L/E	0.7877	likely_pathogenic	0.7937	pathogenic	-1.285	Destabilizing	0.985	D	0.848	deleterious	None	None	None	None	N
L/F	0.2216	likely_benign	0.1995	benign	-1.099	Destabilizing	0.971	D	0.655	prob.neutral	None	None	None	None	N
L/G	0.904	likely_pathogenic	0.9062	pathogenic	-2.504	Highly Destabilizing	0.985	D	0.84	deleterious	None	None	None	None	N
L/H	0.5054	ambiguous	0.4751	ambiguous	-1.611	Destabilizing	0.999	D	0.816	deleterious	None	None	None	None	N
L/I	0.0727	likely_benign	0.0763	benign	-0.683	Destabilizing	0.022	N	0.289	neutral	N	0.428107555	None	None	N
L/K	0.6565	likely_pathogenic	0.616	pathogenic	-1.521	Destabilizing	0.985	D	0.803	deleterious	None	None	None	None	N
L/M	0.1363	likely_benign	0.1438	benign	-0.685	Destabilizing	0.971	D	0.632	neutral	None	None	None	None	N
L/N	0.8262	likely_pathogenic	0.8275	pathogenic	-1.726	Destabilizing	0.995	D	0.835	deleterious	None	None	None	None	N
L/P	0.9597	likely_pathogenic	0.9524	pathogenic	-1.103	Destabilizing	0.994	D	0.846	deleterious	N	0.460769179	None	None	N
L/Q	0.4138	ambiguous	0.4016	ambiguous	-1.636	Destabilizing	0.994	D	0.8	deleterious	N	0.456691164	None	None	N
L/R	0.5127	ambiguous	0.4714	ambiguous	-1.165	Destabilizing	0.994	D	0.813	deleterious	N	0.450411941	None	None	N
L/S	0.6918	likely_pathogenic	0.7131	pathogenic	-2.499	Highly Destabilizing	0.985	D	0.795	deleterious	None	None	None	None	N
L/T	0.3893	ambiguous	0.4584	ambiguous	-2.177	Highly Destabilizing	0.971	D	0.736	deleterious	None	None	None	None	N
L/V	0.0835	likely_benign	0.0882	benign	-1.103	Destabilizing	0.022	N	0.256	neutral	N	0.41310519	None	None	N
L/W	0.5969	likely_pathogenic	0.5506	ambiguous	-1.283	Destabilizing	0.999	D	0.733	deleterious	None	None	None	None	N
L/Y	0.6197	likely_pathogenic	0.5829	pathogenic	-1.02	Destabilizing	0.995	D	0.707	prob.delet.	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.