TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30105	90538;90539;90540	chr2:178552587;178552586;178552585	chr2:179417314;179417313;179417312
N2AB	28464	85615;85616;85617	chr2:178552587;178552586;178552585	chr2:179417314;179417313;179417312
N2A	27537	82834;82835;82836	chr2:178552587;178552586;178552585	chr2:179417314;179417313;179417312
N2B	21040	63343;63344;63345	chr2:178552587;178552586;178552585	chr2:179417314;179417313;179417312
Novex-1	21165	63718;63719;63720	chr2:178552587;178552586;178552585	chr2:179417314;179417313;179417312
Novex-2	21232	63919;63920;63921	chr2:178552587;178552586;178552585	chr2:179417314;179417313;179417312
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-107
• Domain position: 76
• Structural Position: 110
• Q(SASA): 0.0709
• 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
A/T	rs1699867864	None	0.993	D	0.735	0.582	0.50685403127	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
A/T	rs1699867864	None	0.993	D	0.735	0.582	0.50685403127	gnomAD-4.0.0	1.85905E-06	None	None	None	None	N	None	2.66923E-05	0	None	3.37838E-05	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
A/C	0.7784	likely_pathogenic	0.7248	pathogenic	-1.701	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
A/D	0.9971	likely_pathogenic	0.9959	pathogenic	-2.888	Highly Destabilizing	0.997	D	0.875	deleterious	D	0.56383793	None	None	N
A/E	0.9938	likely_pathogenic	0.9928	pathogenic	-2.631	Highly Destabilizing	0.995	D	0.803	deleterious	None	None	None	None	N
A/F	0.9891	likely_pathogenic	0.9863	pathogenic	-0.87	Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
A/G	0.4189	ambiguous	0.3497	ambiguous	-2.391	Highly Destabilizing	0.977	D	0.613	neutral	D	0.53064116	None	None	N
A/H	0.9952	likely_pathogenic	0.9945	pathogenic	-2.323	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
A/I	0.9606	likely_pathogenic	0.9448	pathogenic	-0.592	Destabilizing	0.998	D	0.852	deleterious	None	None	None	None	N
A/K	0.9984	likely_pathogenic	0.9984	pathogenic	-1.472	Destabilizing	0.995	D	0.829	deleterious	None	None	None	None	N
A/L	0.8877	likely_pathogenic	0.8732	pathogenic	-0.592	Destabilizing	0.983	D	0.793	deleterious	None	None	None	None	N
A/M	0.9588	likely_pathogenic	0.94	pathogenic	-1.082	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
A/N	0.9889	likely_pathogenic	0.9853	pathogenic	-1.966	Destabilizing	0.998	D	0.883	deleterious	None	None	None	None	N
A/P	0.9263	likely_pathogenic	0.9382	pathogenic	-1.003	Destabilizing	0.235	N	0.538	neutral	D	0.537339884	None	None	N
A/Q	0.9817	likely_pathogenic	0.9814	pathogenic	-1.658	Destabilizing	0.998	D	0.86	deleterious	None	None	None	None	N
A/R	0.9918	likely_pathogenic	0.9927	pathogenic	-1.601	Destabilizing	0.998	D	0.855	deleterious	None	None	None	None	N
A/S	0.234	likely_benign	0.1695	benign	-2.349	Highly Destabilizing	0.977	D	0.627	neutral	N	0.51133191	None	None	N
A/T	0.6437	likely_pathogenic	0.5223	ambiguous	-1.975	Destabilizing	0.993	D	0.735	prob.delet.	D	0.530321537	None	None	N
A/V	0.8023	likely_pathogenic	0.7347	pathogenic	-1.003	Destabilizing	0.989	D	0.701	prob.neutral	D	0.543616854	None	None	N
A/W	0.9987	likely_pathogenic	0.9985	pathogenic	-1.486	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
A/Y	0.9959	likely_pathogenic	0.9951	pathogenic	-1.18	Destabilizing	1.0	D	0.909	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.