TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20988	63187;63188;63189	chr2:178588763;178588762;178588761	chr2:179453490;179453489;179453488
N2AB	19347	58264;58265;58266	chr2:178588763;178588762;178588761	chr2:179453490;179453489;179453488
N2A	18420	55483;55484;55485	chr2:178588763;178588762;178588761	chr2:179453490;179453489;179453488
N2B	11923	35992;35993;35994	chr2:178588763;178588762;178588761	chr2:179453490;179453489;179453488
Novex-1	12048	36367;36368;36369	chr2:178588763;178588762;178588761	chr2:179453490;179453489;179453488
Novex-2	12115	36568;36569;36570	chr2:178588763;178588762;178588761	chr2:179453490;179453489;179453488
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: Fn3-40
• Domain position: 26
• Structural Position: 28
• Q(SASA): 0.9875
• Predicted PPI site: I

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/A	rs2049605788	None	0.989	N	0.575	0.338	0.380730819819	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	1.93949E-04	None	0	0	0	0	0
E/A	rs2049605788	None	0.989	N	0.575	0.338	0.380730819819	gnomAD-4.0.0	1.41002E-05	None	None	None	None	I	None	0	0	None	0	2.67575E-04	None	0	0	0	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
E/A	0.125	likely_benign	0.1282	benign	-0.031	Destabilizing	0.989	D	0.575	neutral	N	0.472458511	None	None	I
E/C	0.7487	likely_pathogenic	0.7584	pathogenic	-0.354	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	I
E/D	0.1352	likely_benign	0.1469	benign	-0.457	Destabilizing	0.994	D	0.514	neutral	N	0.47638425	None	None	I
E/F	0.7138	likely_pathogenic	0.7301	pathogenic	-0.065	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
E/G	0.1899	likely_benign	0.2007	benign	-0.131	Destabilizing	0.217	N	0.393	neutral	N	0.464764534	None	None	I
E/H	0.4578	ambiguous	0.4761	ambiguous	0.613	Stabilizing	1.0	D	0.662	neutral	None	None	None	None	I
E/I	0.2597	likely_benign	0.2592	benign	0.174	Stabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
E/K	0.1604	likely_benign	0.1693	benign	0.326	Stabilizing	0.994	D	0.603	neutral	N	0.474997383	None	None	I
E/L	0.3208	likely_benign	0.3261	benign	0.174	Stabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	I
E/M	0.3872	ambiguous	0.4063	ambiguous	-0.121	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	I
E/N	0.267	likely_benign	0.2835	benign	0.033	Stabilizing	0.999	D	0.628	neutral	None	None	None	None	I
E/P	0.4451	ambiguous	0.429	ambiguous	0.123	Stabilizing	1.0	D	0.642	neutral	None	None	None	None	I
E/Q	0.1338	likely_benign	0.137	benign	0.038	Stabilizing	0.999	D	0.614	neutral	N	0.512459693	None	None	I
E/R	0.2436	likely_benign	0.2536	benign	0.588	Stabilizing	1.0	D	0.668	neutral	None	None	None	None	I
E/S	0.1877	likely_benign	0.1933	benign	-0.08	Destabilizing	0.992	D	0.607	neutral	None	None	None	None	I
E/T	0.1961	likely_benign	0.1971	benign	0.014	Stabilizing	0.999	D	0.595	neutral	None	None	None	None	I
E/V	0.1628	likely_benign	0.1656	benign	0.123	Stabilizing	0.999	D	0.647	neutral	N	0.487217319	None	None	I
E/W	0.8624	likely_pathogenic	0.8744	pathogenic	-0.022	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	I
E/Y	0.58	likely_pathogenic	0.5934	pathogenic	0.153	Stabilizing	1.0	D	0.651	neutral	None	None	None	None	I

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.