TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23418	70477;70478;70479	chr2:178575880;178575879;178575878	chr2:179440607;179440606;179440605
N2AB	21777	65554;65555;65556	chr2:178575880;178575879;178575878	chr2:179440607;179440606;179440605
N2A	20850	62773;62774;62775	chr2:178575880;178575879;178575878	chr2:179440607;179440606;179440605
N2B	14353	43282;43283;43284	chr2:178575880;178575879;178575878	chr2:179440607;179440606;179440605
Novex-1	14478	43657;43658;43659	chr2:178575880;178575879;178575878	chr2:179440607;179440606;179440605
Novex-2	14545	43858;43859;43860	chr2:178575880;178575879;178575878	chr2:179440607;179440606;179440605
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-129
• Domain position: 74
• Structural Position: 159
• Q(SASA): 0.2096
• 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
E/K	None	None	0.999	N	0.681	0.441	0.466991082792	gnomAD-4.0.0	2.05285E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	3.47842E-05	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
E/A	0.2191	likely_benign	0.2495	benign	-0.518	Destabilizing	0.999	D	0.702	prob.neutral	D	0.532808828	None	None	N
E/C	0.8451	likely_pathogenic	0.883	pathogenic	-0.065	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
E/D	0.3718	ambiguous	0.4124	ambiguous	-0.918	Destabilizing	0.999	D	0.527	neutral	N	0.494811044	None	None	N
E/F	0.8956	likely_pathogenic	0.9317	pathogenic	-0.609	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
E/G	0.3633	ambiguous	0.3986	ambiguous	-0.787	Destabilizing	1.0	D	0.719	prob.delet.	N	0.499192363	None	None	N
E/H	0.5864	likely_pathogenic	0.6777	pathogenic	-0.931	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
E/I	0.4729	ambiguous	0.538	ambiguous	0.18	Stabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
E/K	0.2216	likely_benign	0.2691	benign	-0.144	Destabilizing	0.999	D	0.681	prob.neutral	N	0.478896985	None	None	N
E/L	0.6179	likely_pathogenic	0.6994	pathogenic	0.18	Stabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
E/M	0.5352	ambiguous	0.6104	pathogenic	0.593	Stabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
E/N	0.4415	ambiguous	0.5057	ambiguous	-0.385	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
E/P	0.9931	likely_pathogenic	0.9954	pathogenic	-0.031	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
E/Q	0.1367	likely_benign	0.155	benign	-0.344	Destabilizing	1.0	D	0.686	prob.neutral	N	0.516820655	None	None	N
E/R	0.383	ambiguous	0.4653	ambiguous	-0.13	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/S	0.2342	likely_benign	0.273	benign	-0.609	Destabilizing	0.999	D	0.736	prob.delet.	None	None	None	None	N
E/T	0.2187	likely_benign	0.2487	benign	-0.395	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
E/V	0.2876	likely_benign	0.3318	benign	-0.031	Destabilizing	1.0	D	0.765	deleterious	N	0.518783525	None	None	N
E/W	0.9636	likely_pathogenic	0.9776	pathogenic	-0.559	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
E/Y	0.8435	likely_pathogenic	0.891	pathogenic	-0.39	Destabilizing	1.0	D	0.769	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.