TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30865	92818;92819;92820	chr2:178549033;178549032;178549031	chr2:179413760;179413759;179413758
N2AB	29224	87895;87896;87897	chr2:178549033;178549032;178549031	chr2:179413760;179413759;179413758
N2A	28297	85114;85115;85116	chr2:178549033;178549032;178549031	chr2:179413760;179413759;179413758
N2B	21800	65623;65624;65625	chr2:178549033;178549032;178549031	chr2:179413760;179413759;179413758
Novex-1	21925	65998;65999;66000	chr2:178549033;178549032;178549031	chr2:179413760;179413759;179413758
Novex-2	21992	66199;66200;66201	chr2:178549033;178549032;178549031	chr2:179413760;179413759;179413758
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Fn3-113
• Domain position: 45
• Structural Position: 60
• Q(SASA): 0.2991
• 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/F	rs192086736	None	0.996	N	0.583	0.219	0.28722502521	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/F	rs192086736	None	0.996	N	0.583	0.219	0.28722502521	gnomAD-4.0.0	6.57022E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.46977E-05	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	0.0859	likely_benign	0.0815	benign	-0.287	Destabilizing	0.895	D	0.383	neutral	None	None	None	None	N
L/C	0.2936	likely_benign	0.3023	benign	-0.325	Destabilizing	0.999	D	0.637	neutral	None	None	None	None	N
L/D	0.2712	likely_benign	0.2599	benign	-0.165	Destabilizing	0.968	D	0.668	neutral	None	None	None	None	N
L/E	0.1464	likely_benign	0.1387	benign	-0.283	Destabilizing	0.11	N	0.451	neutral	None	None	None	None	N
L/F	0.1094	likely_benign	0.1026	benign	-0.571	Destabilizing	0.996	D	0.583	neutral	N	0.446138701	None	None	N
L/G	0.2258	likely_benign	0.2234	benign	-0.406	Destabilizing	0.983	D	0.671	neutral	None	None	None	None	N
L/H	0.1181	likely_benign	0.1091	benign	0.101	Stabilizing	0.998	D	0.719	prob.delet.	None	None	None	None	N
L/I	0.0823	likely_benign	0.077	benign	-0.108	Destabilizing	0.963	D	0.355	neutral	N	0.464551103	None	None	N
L/K	0.1313	likely_benign	0.1267	benign	-0.046	Destabilizing	0.968	D	0.549	neutral	None	None	None	None	N
L/M	0.0831	likely_benign	0.0795	benign	-0.159	Destabilizing	0.997	D	0.595	neutral	None	None	None	None	N
L/N	0.1579	likely_benign	0.1498	benign	0.259	Stabilizing	0.983	D	0.707	prob.neutral	None	None	None	None	N
L/P	0.33	likely_benign	0.3453	ambiguous	-0.136	Destabilizing	0.992	D	0.715	prob.delet.	None	None	None	None	N
L/Q	0.0789	likely_benign	0.0752	benign	None	Stabilizing	0.968	D	0.609	neutral	None	None	None	None	N
L/R	0.1092	likely_benign	0.1081	benign	0.454	Stabilizing	0.983	D	0.608	neutral	None	None	None	None	N
L/S	0.0911	likely_benign	0.0858	benign	-0.111	Destabilizing	0.957	D	0.553	neutral	N	0.313995361	None	None	N
L/T	0.0794	likely_benign	0.0729	benign	-0.127	Destabilizing	0.983	D	0.544	neutral	None	None	None	None	N
L/V	0.0757	likely_benign	0.0713	benign	-0.136	Destabilizing	0.928	D	0.325	neutral	N	0.399019545	None	None	N
L/W	0.1892	likely_benign	0.1945	benign	-0.615	Destabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	N
L/Y	0.2315	likely_benign	0.2289	benign	-0.315	Destabilizing	0.997	D	0.616	neutral	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.