TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26686	80281;80282;80283	chr2:178566076;178566075;178566074	chr2:179430803;179430802;179430801
N2AB	25045	75358;75359;75360	chr2:178566076;178566075;178566074	chr2:179430803;179430802;179430801
N2A	24118	72577;72578;72579	chr2:178566076;178566075;178566074	chr2:179430803;179430802;179430801
N2B	17621	53086;53087;53088	chr2:178566076;178566075;178566074	chr2:179430803;179430802;179430801
Novex-1	17746	53461;53462;53463	chr2:178566076;178566075;178566074	chr2:179430803;179430802;179430801
Novex-2	17813	53662;53663;53664	chr2:178566076;178566075;178566074	chr2:179430803;179430802;179430801
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-82
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.243
• 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
P/L	rs867306848	-0.669	0.999	N	0.826	0.424	0.657421573829	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
P/L	rs867306848	-0.669	0.999	N	0.826	0.424	0.657421573829	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
P/L	rs867306848	-0.669	0.999	N	0.826	0.424	0.657421573829	gnomAD-4.0.0	6.57549E-06	None	None	None	None	I	None	2.41464E-05	0	None	0	0	None	0	0	0	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
P/A	0.0791	likely_benign	0.091	benign	-1.714	Destabilizing	0.227	N	0.406	neutral	N	0.447269277	None	None	I
P/C	0.4543	ambiguous	0.5081	ambiguous	-1.077	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	I
P/D	0.8233	likely_pathogenic	0.8271	pathogenic	-1.906	Destabilizing	0.98	D	0.829	deleterious	None	None	None	None	I
P/E	0.4799	ambiguous	0.5049	ambiguous	-1.883	Destabilizing	0.988	D	0.82	deleterious	None	None	None	None	I
P/F	0.5789	likely_pathogenic	0.6099	pathogenic	-1.26	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	I
P/G	0.4361	ambiguous	0.4744	ambiguous	-2.053	Highly Destabilizing	0.973	D	0.791	deleterious	None	None	None	None	I
P/H	0.3488	ambiguous	0.3548	ambiguous	-1.643	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
P/I	0.3724	ambiguous	0.4368	ambiguous	-0.857	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	I
P/K	0.3717	ambiguous	0.4095	ambiguous	-1.435	Destabilizing	0.999	D	0.82	deleterious	None	None	None	None	I
P/L	0.1883	likely_benign	0.2185	benign	-0.857	Destabilizing	0.999	D	0.826	deleterious	N	0.520191502	None	None	I
P/M	0.3345	likely_benign	0.3851	ambiguous	-0.64	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	I
P/N	0.5643	likely_pathogenic	0.6075	pathogenic	-1.259	Destabilizing	0.999	D	0.871	deleterious	None	None	None	None	I
P/Q	0.2232	likely_benign	0.2421	benign	-1.426	Destabilizing	1.0	D	0.83	deleterious	N	0.506896186	None	None	I
P/R	0.2826	likely_benign	0.3058	benign	-0.909	Destabilizing	0.999	D	0.869	deleterious	N	0.503782314	None	None	I
P/S	0.1757	likely_benign	0.191	benign	-1.747	Destabilizing	0.974	D	0.781	deleterious	N	0.49166554	None	None	I
P/T	0.1969	likely_benign	0.2294	benign	-1.626	Destabilizing	0.992	D	0.819	deleterious	N	0.508163633	None	None	I
P/V	0.2601	likely_benign	0.3105	benign	-1.111	Destabilizing	0.995	D	0.833	deleterious	None	None	None	None	I
P/W	0.8254	likely_pathogenic	0.8239	pathogenic	-1.518	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	I
P/Y	0.6027	likely_pathogenic	0.6267	pathogenic	-1.239	Destabilizing	1.0	D	0.869	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.