TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18072	54439;54440;54441	chr2:178604875;178604874;178604873	chr2:179469602;179469601;179469600
N2AB	16431	49516;49517;49518	chr2:178604875;178604874;178604873	chr2:179469602;179469601;179469600
N2A	15504	46735;46736;46737	chr2:178604875;178604874;178604873	chr2:179469602;179469601;179469600
N2B	9007	27244;27245;27246	chr2:178604875;178604874;178604873	chr2:179469602;179469601;179469600
Novex-1	9132	27619;27620;27621	chr2:178604875;178604874;178604873	chr2:179469602;179469601;179469600
Novex-2	9199	27820;27821;27822	chr2:178604875;178604874;178604873	chr2:179469602;179469601;179469600
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-19
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.2263
• 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/H	None	None	1.0	N	0.857	0.536	0.868193264195	gnomAD-4.0.0	1.59502E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86436E-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
L/A	0.8839	likely_pathogenic	0.9065	pathogenic	-2.448	Highly Destabilizing	0.994	D	0.689	prob.neutral	None	None	None	None	N
L/C	0.892	likely_pathogenic	0.9003	pathogenic	-2.064	Highly Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
L/D	0.9991	likely_pathogenic	0.9992	pathogenic	-2.778	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
L/E	0.995	likely_pathogenic	0.9954	pathogenic	-2.612	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
L/F	0.5463	ambiguous	0.5686	pathogenic	-1.551	Destabilizing	0.999	D	0.854	deleterious	D	0.528976302	None	None	N
L/G	0.99	likely_pathogenic	0.9911	pathogenic	-2.946	Highly Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
L/H	0.989	likely_pathogenic	0.9898	pathogenic	-2.376	Highly Destabilizing	1.0	D	0.857	deleterious	N	0.515531737	None	None	N
L/I	0.1104	likely_benign	0.1245	benign	-1.039	Destabilizing	0.962	D	0.716	prob.delet.	N	0.471890868	None	None	N
L/K	0.9906	likely_pathogenic	0.9919	pathogenic	-1.837	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
L/M	0.2813	likely_benign	0.2799	benign	-1.135	Destabilizing	0.999	D	0.817	deleterious	None	None	None	None	N
L/N	0.994	likely_pathogenic	0.9945	pathogenic	-2.059	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
L/P	0.8995	likely_pathogenic	0.9315	pathogenic	-1.487	Destabilizing	1.0	D	0.862	deleterious	N	0.46388746	None	None	N
L/Q	0.9843	likely_pathogenic	0.985	pathogenic	-2.027	Highly Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
L/R	0.983	likely_pathogenic	0.9845	pathogenic	-1.482	Destabilizing	1.0	D	0.855	deleterious	N	0.504175432	None	None	N
L/S	0.9881	likely_pathogenic	0.9902	pathogenic	-2.747	Highly Destabilizing	0.999	D	0.842	deleterious	None	None	None	None	N
L/T	0.869	likely_pathogenic	0.881	pathogenic	-2.439	Highly Destabilizing	0.998	D	0.813	deleterious	None	None	None	None	N
L/V	0.1222	likely_benign	0.1349	benign	-1.487	Destabilizing	0.619	D	0.379	neutral	N	0.425152927	None	None	N
L/W	0.9543	likely_pathogenic	0.9629	pathogenic	-1.871	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
L/Y	0.9676	likely_pathogenic	0.9736	pathogenic	-1.598	Destabilizing	1.0	D	0.829	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.