TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23729	71410;71411;71412	chr2:178574947;178574946;178574945	chr2:179439674;179439673;179439672
N2AB	22088	66487;66488;66489	chr2:178574947;178574946;178574945	chr2:179439674;179439673;179439672
N2A	21161	63706;63707;63708	chr2:178574947;178574946;178574945	chr2:179439674;179439673;179439672
N2B	14664	44215;44216;44217	chr2:178574947;178574946;178574945	chr2:179439674;179439673;179439672
Novex-1	14789	44590;44591;44592	chr2:178574947;178574946;178574945	chr2:179439674;179439673;179439672
Novex-2	14856	44791;44792;44793	chr2:178574947;178574946;178574945	chr2:179439674;179439673;179439672
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: Fn3-60
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.4989
• 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
P/R	None	None	0.999	N	0.887	0.43	0.525258673147	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
P/T	None	None	0.993	N	0.799	0.342	0.450539155747	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
P/A	0.1231	likely_benign	0.1204	benign	-1.587	Destabilizing	0.977	D	0.775	deleterious	N	0.49267628	None	None	N
P/C	0.597	likely_pathogenic	0.5227	ambiguous	-1.103	Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
P/D	0.8812	likely_pathogenic	0.8157	pathogenic	-1.709	Destabilizing	0.999	D	0.823	deleterious	None	None	None	None	N
P/E	0.522	ambiguous	0.437	ambiguous	-1.723	Destabilizing	0.999	D	0.817	deleterious	None	None	None	None	N
P/F	0.6645	likely_pathogenic	0.5796	pathogenic	-1.305	Destabilizing	0.999	D	0.885	deleterious	None	None	None	None	N
P/G	0.7034	likely_pathogenic	0.6409	pathogenic	-1.886	Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	N
P/H	0.4557	ambiguous	0.3758	ambiguous	-1.414	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
P/I	0.2508	likely_benign	0.2003	benign	-0.863	Destabilizing	0.483	N	0.65	neutral	None	None	None	None	N
P/K	0.4422	ambiguous	0.3611	ambiguous	-1.271	Destabilizing	0.998	D	0.817	deleterious	None	None	None	None	N
P/L	0.1918	likely_benign	0.1528	benign	-0.863	Destabilizing	0.955	D	0.84	deleterious	N	0.496207763	None	None	N
P/M	0.3531	ambiguous	0.3002	benign	-0.663	Destabilizing	0.999	D	0.887	deleterious	None	None	None	None	N
P/N	0.7062	likely_pathogenic	0.625	pathogenic	-1.064	Destabilizing	0.999	D	0.883	deleterious	None	None	None	None	N
P/Q	0.2875	likely_benign	0.2447	benign	-1.296	Destabilizing	0.999	D	0.861	deleterious	N	0.487813972	None	None	N
P/R	0.3629	ambiguous	0.2892	benign	-0.719	Destabilizing	0.999	D	0.887	deleterious	N	0.492613365	None	None	N
P/S	0.3074	likely_benign	0.2664	benign	-1.544	Destabilizing	0.997	D	0.805	deleterious	N	0.482382695	None	None	N
P/T	0.2353	likely_benign	0.1989	benign	-1.461	Destabilizing	0.993	D	0.799	deleterious	N	0.496714742	None	None	N
P/V	0.2185	likely_benign	0.1714	benign	-1.071	Destabilizing	0.966	D	0.813	deleterious	None	None	None	None	N
P/W	0.8983	likely_pathogenic	0.8223	pathogenic	-1.472	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
P/Y	0.6962	likely_pathogenic	0.5977	pathogenic	-1.196	Destabilizing	1.0	D	0.891	deleterious	None	None	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.