TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17652	53179;53180;53181	chr2:178607833;178607832;178607831	chr2:179472560;179472559;179472558
N2AB	16011	48256;48257;48258	chr2:178607833;178607832;178607831	chr2:179472560;179472559;179472558
N2A	15084	45475;45476;45477	chr2:178607833;178607832;178607831	chr2:179472560;179472559;179472558
N2B	8587	25984;25985;25986	chr2:178607833;178607832;178607831	chr2:179472560;179472559;179472558
Novex-1	8712	26359;26360;26361	chr2:178607833;178607832;178607831	chr2:179472560;179472559;179472558
Novex-2	8779	26560;26561;26562	chr2:178607833;178607832;178607831	chr2:179472560;179472559;179472558
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: Fn3-16
• Domain position: 84
• Structural Position: 117
• Q(SASA): 0.7178
• 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	None	None	0.999	N	0.717	0.329	0.306695030598	gnomAD-4.0.0	1.59287E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86121E-06	0	0
E/D	rs1325497507	-0.223	0.999	N	0.597	0.112	0.199424873507	gnomAD-2.1.1	8.05E-06	None	None	None	None	I	None	0	5.8E-05	None	0	0	None	0	None	0	0	0
E/D	rs1325497507	-0.223	0.999	N	0.597	0.112	0.199424873507	gnomAD-4.0.0	3.18571E-06	None	None	None	None	I	None	0	4.57519E-05	None	0	0	None	0	0	0	0	0
E/K	None	None	0.999	N	0.711	0.264	0.289098819767	gnomAD-4.0.0	3.18571E-06	None	None	None	None	I	None	0	0	None	0	0	None	1.88239E-05	0	0	1.43308E-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	0.1511	likely_benign	0.1438	benign	-0.558	Destabilizing	0.999	D	0.717	prob.delet.	N	0.450149293	None	None	I
E/C	0.7958	likely_pathogenic	0.7825	pathogenic	-0.18	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
E/D	0.3086	likely_benign	0.2931	benign	-0.527	Destabilizing	0.999	D	0.597	neutral	N	0.485512661	None	None	I
E/F	0.713	likely_pathogenic	0.6921	pathogenic	-0.217	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
E/G	0.3023	likely_benign	0.2885	benign	-0.809	Destabilizing	1.0	D	0.747	deleterious	N	0.508197519	None	None	I
E/H	0.5386	ambiguous	0.5258	ambiguous	-0.066	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	I
E/I	0.236	likely_benign	0.2141	benign	0.089	Stabilizing	1.0	D	0.764	deleterious	None	None	None	None	I
E/K	0.1374	likely_benign	0.1234	benign	0.184	Stabilizing	0.999	D	0.711	prob.delet.	N	0.46888977	None	None	I
E/L	0.343	ambiguous	0.3176	benign	0.089	Stabilizing	1.0	D	0.763	deleterious	None	None	None	None	I
E/M	0.3874	ambiguous	0.36	ambiguous	0.242	Stabilizing	1.0	D	0.784	deleterious	None	None	None	None	I
E/N	0.4357	ambiguous	0.398	ambiguous	-0.312	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	I
E/P	0.4249	ambiguous	0.4459	ambiguous	-0.106	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	I
E/Q	0.1485	likely_benign	0.1453	benign	-0.24	Destabilizing	1.0	D	0.721	prob.delet.	N	0.42454156	None	None	I
E/R	0.2443	likely_benign	0.2381	benign	0.452	Stabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
E/S	0.2996	likely_benign	0.2808	benign	-0.477	Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	I
E/T	0.2562	likely_benign	0.2347	benign	-0.264	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
E/V	0.1426	likely_benign	0.1351	benign	-0.106	Destabilizing	1.0	D	0.785	deleterious	N	0.430235381	None	None	I
E/W	0.9035	likely_pathogenic	0.9003	pathogenic	0.024	Stabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
E/Y	0.6585	likely_pathogenic	0.6405	pathogenic	0.05	Stabilizing	1.0	D	0.777	deleterious	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.