TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25828	77707;77708;77709	chr2:178568650;178568649;178568648	chr2:179433377;179433376;179433375
N2AB	24187	72784;72785;72786	chr2:178568650;178568649;178568648	chr2:179433377;179433376;179433375
N2A	23260	70003;70004;70005	chr2:178568650;178568649;178568648	chr2:179433377;179433376;179433375
N2B	16763	50512;50513;50514	chr2:178568650;178568649;178568648	chr2:179433377;179433376;179433375
Novex-1	16888	50887;50888;50889	chr2:178568650;178568649;178568648	chr2:179433377;179433376;179433375
Novex-2	16955	51088;51089;51090	chr2:178568650;178568649;178568648	chr2:179433377;179433376;179433375
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-136
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.4635
• 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
T/N	rs763550644	-0.467	0.331	D	0.48	0.197	None	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	0	0	None	0	1.67448E-04	None	0	None	0	0	0
T/N	rs763550644	-0.467	0.331	D	0.48	0.197	None	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	0	0	0	0	3.87297E-04	None	0	0	0	0	0
T/N	rs763550644	-0.467	0.331	D	0.48	0.197	None	gnomAD-4.0.0	4.15314E-05	None	None	None	None	I	None	0	0	None	0	1.47256E-03	None	0	0	0	0	1.60159E-05

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
T/A	0.059	likely_benign	0.0577	benign	-0.541	Destabilizing	0.001	N	0.229	neutral	N	0.510374686	None	None	I
T/C	0.2897	likely_benign	0.2701	benign	-0.345	Destabilizing	0.909	D	0.635	neutral	None	None	None	None	I
T/D	0.2963	likely_benign	0.2676	benign	-0.057	Destabilizing	0.157	N	0.571	neutral	None	None	None	None	I
T/E	0.2216	likely_benign	0.2058	benign	-0.088	Destabilizing	0.001	N	0.339	neutral	None	None	None	None	I
T/F	0.1941	likely_benign	0.1737	benign	-0.755	Destabilizing	0.726	D	0.724	prob.delet.	None	None	None	None	I
T/G	0.1668	likely_benign	0.157	benign	-0.759	Destabilizing	0.157	N	0.578	neutral	None	None	None	None	I
T/H	0.1876	likely_benign	0.1758	benign	-1.058	Destabilizing	0.909	D	0.714	prob.delet.	None	None	None	None	I
T/I	0.1028	likely_benign	0.0912	benign	-0.07	Destabilizing	0.497	N	0.617	neutral	N	0.49051863	None	None	I
T/K	0.1411	likely_benign	0.1276	benign	-0.661	Destabilizing	0.157	N	0.573	neutral	None	None	None	None	I
T/L	0.0775	likely_benign	0.0725	benign	-0.07	Destabilizing	0.157	N	0.515	neutral	None	None	None	None	I
T/M	0.0849	likely_benign	0.0802	benign	0.102	Stabilizing	0.909	D	0.625	neutral	None	None	None	None	I
T/N	0.0921	likely_benign	0.0832	benign	-0.513	Destabilizing	0.331	N	0.48	neutral	D	0.536406494	None	None	I
T/P	0.3464	ambiguous	0.3315	benign	-0.195	Destabilizing	0.497	N	0.615	neutral	N	0.52130909	None	None	I
T/Q	0.1545	likely_benign	0.1452	benign	-0.671	Destabilizing	0.396	N	0.628	neutral	None	None	None	None	I
T/R	0.1361	likely_benign	0.1246	benign	-0.411	Destabilizing	0.567	D	0.617	neutral	None	None	None	None	I
T/S	0.0824	likely_benign	0.0781	benign	-0.729	Destabilizing	0.001	N	0.283	neutral	N	0.521954329	None	None	I
T/V	0.0809	likely_benign	0.0766	benign	-0.195	Destabilizing	0.157	N	0.407	neutral	None	None	None	None	I
T/W	0.5944	likely_pathogenic	0.5521	ambiguous	-0.749	Destabilizing	0.968	D	0.734	prob.delet.	None	None	None	None	I
T/Y	0.2323	likely_benign	0.2173	benign	-0.5	Destabilizing	0.726	D	0.725	prob.delet.	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.