TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2609	8050;8051;8052	chr2:178773139;178773138;178773137	chr2:179637866;179637865;179637864
N2AB	2609	8050;8051;8052	chr2:178773139;178773138;178773137	chr2:179637866;179637865;179637864
N2A	2609	8050;8051;8052	chr2:178773139;178773138;178773137	chr2:179637866;179637865;179637864
N2B	2563	7912;7913;7914	chr2:178773139;178773138;178773137	chr2:179637866;179637865;179637864
Novex-1	2563	7912;7913;7914	chr2:178773139;178773138;178773137	chr2:179637866;179637865;179637864
Novex-2	2563	7912;7913;7914	chr2:178773139;178773138;178773137	chr2:179637866;179637865;179637864
Novex-3	2609	8050;8051;8052	chr2:178773139;178773138;178773137	chr2:179637866;179637865;179637864

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-15
• Domain position: 77
• Structural Position: 162
• Q(SASA): 0.4079
• 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
N/D	None	None	0.425	N	0.279	0.179	0.241664281697	gnomAD-4.0.0	1.59106E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85719E-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
N/A	0.2197	likely_benign	0.2088	benign	-0.516	Destabilizing	0.495	N	0.366	neutral	None	None	None	None	I
N/C	0.2279	likely_benign	0.2107	benign	0.235	Stabilizing	0.995	D	0.421	neutral	None	None	None	None	I
N/D	0.2095	likely_benign	0.1991	benign	0.142	Stabilizing	0.425	N	0.279	neutral	N	0.345786365	None	None	I
N/E	0.2908	likely_benign	0.275	benign	0.177	Stabilizing	0.176	N	0.206	neutral	None	None	None	None	I
N/F	0.4372	ambiguous	0.3999	ambiguous	-0.501	Destabilizing	0.981	D	0.46	neutral	None	None	None	None	I
N/G	0.406	ambiguous	0.3882	ambiguous	-0.79	Destabilizing	0.495	N	0.265	neutral	None	None	None	None	I
N/H	0.0807	likely_benign	0.075	benign	-0.678	Destabilizing	0.927	D	0.35	neutral	N	0.443142171	None	None	I
N/I	0.1759	likely_benign	0.1586	benign	0.143	Stabilizing	0.927	D	0.484	neutral	N	0.398928474	None	None	I
N/K	0.1869	likely_benign	0.1764	benign	-0.05	Destabilizing	0.001	N	0.073	neutral	N	0.339726353	None	None	I
N/L	0.228	likely_benign	0.213	benign	0.143	Stabilizing	0.704	D	0.449	neutral	None	None	None	None	I
N/M	0.2633	likely_benign	0.2412	benign	0.395	Stabilizing	0.981	D	0.431	neutral	None	None	None	None	I
N/P	0.9407	likely_pathogenic	0.9415	pathogenic	-0.047	Destabilizing	0.828	D	0.469	neutral	None	None	None	None	I
N/Q	0.2169	likely_benign	0.2033	benign	-0.46	Destabilizing	0.013	N	0.061	neutral	None	None	None	None	I
N/R	0.2449	likely_benign	0.228	benign	-0.108	Destabilizing	0.329	N	0.258	neutral	None	None	None	None	I
N/S	0.1143	likely_benign	0.1078	benign	-0.423	Destabilizing	0.425	N	0.291	neutral	N	0.40034829	None	None	I
N/T	0.1238	likely_benign	0.1187	benign	-0.213	Destabilizing	0.425	N	0.233	neutral	N	0.371621112	None	None	I
N/V	0.1911	likely_benign	0.1742	benign	-0.047	Destabilizing	0.828	D	0.456	neutral	None	None	None	None	I
N/W	0.7141	likely_pathogenic	0.6894	pathogenic	-0.363	Destabilizing	0.995	D	0.434	neutral	None	None	None	None	I
N/Y	0.1056	likely_benign	0.0972	benign	-0.141	Destabilizing	0.975	D	0.468	neutral	N	0.457475873	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.