TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20180	60763;60764;60765	chr2:178591187;178591186;178591185	chr2:179455914;179455913;179455912
N2AB	18539	55840;55841;55842	chr2:178591187;178591186;178591185	chr2:179455914;179455913;179455912
N2A	17612	53059;53060;53061	chr2:178591187;178591186;178591185	chr2:179455914;179455913;179455912
N2B	11115	33568;33569;33570	chr2:178591187;178591186;178591185	chr2:179455914;179455913;179455912
Novex-1	11240	33943;33944;33945	chr2:178591187;178591186;178591185	chr2:179455914;179455913;179455912
Novex-2	11307	34144;34145;34146	chr2:178591187;178591186;178591185	chr2:179455914;179455913;179455912
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-34
• Domain position: 10
• Structural Position: 11
• Q(SASA): 0.323
• 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
N/H	rs1030296243	-0.787	0.003	N	0.317	0.079	0.0611884634855	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
N/H	rs1030296243	-0.787	0.003	N	0.317	0.079	0.0611884634855	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
N/H	rs1030296243	-0.787	0.003	N	0.317	0.079	0.0611884634855	gnomAD-4.0.0	3.71919E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.39112E-06	2.19626E-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
N/A	0.1656	likely_benign	0.1858	benign	-0.572	Destabilizing	0.575	D	0.641	neutral	None	None	None	None	N
N/C	0.1808	likely_benign	0.2161	benign	0.151	Stabilizing	0.991	D	0.789	deleterious	None	None	None	None	N
N/D	0.1138	likely_benign	0.1229	benign	0.245	Stabilizing	0.001	N	0.199	neutral	N	0.461876158	None	None	N
N/E	0.2039	likely_benign	0.2376	benign	0.275	Stabilizing	0.404	N	0.501	neutral	None	None	None	None	N
N/F	0.4393	ambiguous	0.5388	ambiguous	-0.629	Destabilizing	0.906	D	0.783	deleterious	None	None	None	None	N
N/G	0.2939	likely_benign	0.3519	ambiguous	-0.828	Destabilizing	0.575	D	0.499	neutral	None	None	None	None	N
N/H	0.0665	likely_benign	0.0814	benign	-0.642	Destabilizing	0.003	N	0.317	neutral	N	0.502855988	None	None	N
N/I	0.1425	likely_benign	0.1651	benign	0.039	Stabilizing	0.879	D	0.783	deleterious	N	0.489966836	None	None	N
N/K	0.1599	likely_benign	0.196	benign	0.043	Stabilizing	0.505	D	0.509	neutral	N	0.420930825	None	None	N
N/L	0.1583	likely_benign	0.1981	benign	0.039	Stabilizing	0.826	D	0.733	prob.delet.	None	None	None	None	N
N/M	0.2387	likely_benign	0.2622	benign	0.31	Stabilizing	0.991	D	0.731	prob.delet.	None	None	None	None	N
N/P	0.721	likely_pathogenic	0.8643	pathogenic	-0.135	Destabilizing	0.906	D	0.749	deleterious	None	None	None	None	N
N/Q	0.1742	likely_benign	0.2096	benign	-0.491	Destabilizing	0.826	D	0.569	neutral	None	None	None	None	N
N/R	0.1724	likely_benign	0.2324	benign	0.04	Stabilizing	0.826	D	0.556	neutral	None	None	None	None	N
N/S	0.0814	likely_benign	0.084	benign	-0.458	Destabilizing	0.338	N	0.499	neutral	N	0.465297678	None	None	N
N/T	0.0841	likely_benign	0.0884	benign	-0.247	Destabilizing	0.505	D	0.511	neutral	N	0.456486194	None	None	N
N/V	0.131	likely_benign	0.1493	benign	-0.135	Destabilizing	0.906	D	0.766	deleterious	None	None	None	None	N
N/W	0.6643	likely_pathogenic	0.7653	pathogenic	-0.47	Destabilizing	0.991	D	0.756	deleterious	None	None	None	None	N
N/Y	0.1299	likely_benign	0.1708	benign	-0.242	Destabilizing	0.642	D	0.752	deleterious	N	0.473268115	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.