TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8023	24292;24293;24294	chr2:178719323;178719322;178719321	chr2:179584050;179584049;179584048
N2AB	7706	23341;23342;23343	chr2:178719323;178719322;178719321	chr2:179584050;179584049;179584048
N2A	6779	20560;20561;20562	chr2:178719323;178719322;178719321	chr2:179584050;179584049;179584048
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-65
• Domain position: 39
• Structural Position: 55
• Q(SASA): 0.3807
• 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/K	rs757931022	0.34	0.007	N	0.155	0.152	0.0611884634855	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
N/K	rs757931022	0.34	0.007	N	0.155	0.152	0.0611884634855	gnomAD-4.0.0	2.73875E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.601E-06	0	0
N/S	rs779375050	-0.124	0.007	N	0.137	0.074	0.130388298395	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	8.88E-06	0
N/S	rs779375050	-0.124	0.007	N	0.137	0.074	0.130388298395	gnomAD-4.0.0	1.59124E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43275E-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	0.1285	likely_benign	0.141	benign	-0.354	Destabilizing	0.129	N	0.331	neutral	None	None	None	None	N
N/C	0.1706	likely_benign	0.1734	benign	0.256	Stabilizing	0.983	D	0.345	neutral	None	None	None	None	N
N/D	0.1007	likely_benign	0.1108	benign	0.225	Stabilizing	0.002	N	0.139	neutral	N	0.48688175	None	None	N
N/E	0.1422	likely_benign	0.1619	benign	0.198	Stabilizing	0.01	N	0.143	neutral	None	None	None	None	N
N/F	0.2525	likely_benign	0.2863	benign	-0.72	Destabilizing	0.836	D	0.371	neutral	None	None	None	None	N
N/G	0.1887	likely_benign	0.2059	benign	-0.531	Destabilizing	0.129	N	0.22	neutral	None	None	None	None	N
N/H	0.0681	likely_benign	0.0705	benign	-0.508	Destabilizing	0.794	D	0.3	neutral	N	0.493866438	None	None	N
N/I	0.1007	likely_benign	0.106	benign	0.025	Stabilizing	0.213	N	0.389	neutral	N	0.463428888	None	None	N
N/K	0.0872	likely_benign	0.0959	benign	0.08	Stabilizing	0.007	N	0.155	neutral	N	0.398875977	None	None	N
N/L	0.1237	likely_benign	0.1374	benign	0.025	Stabilizing	0.129	N	0.355	neutral	None	None	None	None	N
N/M	0.1675	likely_benign	0.1785	benign	0.249	Stabilizing	0.836	D	0.355	neutral	None	None	None	None	N
N/P	0.6663	likely_pathogenic	0.704	pathogenic	-0.075	Destabilizing	0.593	D	0.387	neutral	None	None	None	None	N
N/Q	0.1261	likely_benign	0.1365	benign	-0.372	Destabilizing	0.418	N	0.245	neutral	None	None	None	None	N
N/R	0.0992	likely_benign	0.1086	benign	0.122	Stabilizing	0.264	N	0.187	neutral	None	None	None	None	N
N/S	0.0679	likely_benign	0.0708	benign	-0.195	Destabilizing	0.007	N	0.137	neutral	N	0.467773128	None	None	N
N/T	0.0821	likely_benign	0.0851	benign	-0.072	Destabilizing	0.003	N	0.127	neutral	N	0.473605809	None	None	N
N/V	0.1125	likely_benign	0.1189	benign	-0.075	Destabilizing	0.01	N	0.265	neutral	None	None	None	None	N
N/W	0.4488	ambiguous	0.4898	ambiguous	-0.715	Destabilizing	0.983	D	0.38	neutral	None	None	None	None	N
N/Y	0.0899	likely_benign	0.0975	benign	-0.444	Destabilizing	0.921	D	0.36	neutral	N	0.508758532	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.