TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28922	86989;86990;86991	chr2:178559368;178559367;178559366	chr2:179424095;179424094;179424093
N2AB	27281	82066;82067;82068	chr2:178559368;178559367;178559366	chr2:179424095;179424094;179424093
N2A	26354	79285;79286;79287	chr2:178559368;178559367;178559366	chr2:179424095;179424094;179424093
N2B	19857	59794;59795;59796	chr2:178559368;178559367;178559366	chr2:179424095;179424094;179424093
Novex-1	19982	60169;60170;60171	chr2:178559368;178559367;178559366	chr2:179424095;179424094;179424093
Novex-2	20049	60370;60371;60372	chr2:178559368;178559367;178559366	chr2:179424095;179424094;179424093
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: Fn3-98
• Domain position: 78
• Structural Position: 111
• Q(SASA): 0.1934
• 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/Q	rs1178384540	-0.572	0.988	N	0.604	0.174	0.218845423259	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
E/Q	rs1178384540	-0.572	0.988	N	0.604	0.174	0.218845423259	gnomAD-4.0.0	2.73807E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59915E-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
E/A	0.3379	likely_benign	0.4237	ambiguous	-0.765	Destabilizing	0.6	D	0.483	neutral	N	0.511379471	None	None	N
E/C	0.8696	likely_pathogenic	0.915	pathogenic	-0.799	Destabilizing	0.997	D	0.805	deleterious	None	None	None	None	N
E/D	0.6246	likely_pathogenic	0.7092	pathogenic	-1.379	Destabilizing	0.704	D	0.391	neutral	N	0.508564799	None	None	N
E/F	0.9012	likely_pathogenic	0.9456	pathogenic	-1.208	Destabilizing	0.963	D	0.833	deleterious	None	None	None	None	N
E/G	0.4952	ambiguous	0.5971	pathogenic	-1.066	Destabilizing	0.986	D	0.696	prob.neutral	N	0.490460544	None	None	N
E/H	0.7966	likely_pathogenic	0.8755	pathogenic	-1.452	Destabilizing	0.998	D	0.661	neutral	None	None	None	None	N
E/I	0.4724	ambiguous	0.6016	pathogenic	0.043	Stabilizing	0.858	D	0.745	deleterious	None	None	None	None	N
E/K	0.3316	likely_benign	0.4372	ambiguous	-1.238	Destabilizing	0.918	D	0.422	neutral	N	0.519614952	None	None	N
E/L	0.7171	likely_pathogenic	0.8248	pathogenic	0.043	Stabilizing	0.633	D	0.697	prob.neutral	None	None	None	None	N
E/M	0.5934	likely_pathogenic	0.6919	pathogenic	0.485	Stabilizing	0.943	D	0.797	deleterious	None	None	None	None	N
E/N	0.6859	likely_pathogenic	0.7984	pathogenic	-1.335	Destabilizing	0.972	D	0.665	neutral	None	None	None	None	N
E/P	0.9948	likely_pathogenic	0.9968	pathogenic	-0.207	Destabilizing	0.917	D	0.793	deleterious	None	None	None	None	N
E/Q	0.1809	likely_benign	0.2378	benign	-1.135	Destabilizing	0.988	D	0.604	neutral	N	0.517209365	None	None	N
E/R	0.5102	ambiguous	0.6209	pathogenic	-1.279	Destabilizing	0.981	D	0.677	prob.neutral	None	None	None	None	N
E/S	0.4316	ambiguous	0.5434	ambiguous	-1.807	Destabilizing	0.889	D	0.473	neutral	None	None	None	None	N
E/T	0.4734	ambiguous	0.5847	pathogenic	-1.537	Destabilizing	0.951	D	0.701	prob.neutral	None	None	None	None	N
E/V	0.2781	likely_benign	0.359	ambiguous	-0.207	Destabilizing	0.013	N	0.391	neutral	N	0.450458724	None	None	N
E/W	0.974	likely_pathogenic	0.9851	pathogenic	-1.547	Destabilizing	0.999	D	0.788	deleterious	None	None	None	None	N
E/Y	0.8809	likely_pathogenic	0.9318	pathogenic	-1.125	Destabilizing	0.993	D	0.825	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.