TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8532	25819;25820;25821	chr2:178717140;178717139;178717138	chr2:179581867;179581866;179581865
N2AB	8215	24868;24869;24870	chr2:178717140;178717139;178717138	chr2:179581867;179581866;179581865
N2A	7288	22087;22088;22089	chr2:178717140;178717139;178717138	chr2:179581867;179581866;179581865
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-70
• Domain position: 77
• Structural Position: 161
• Q(SASA): 0.192
• 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/S	rs368106359	-0.945	0.999	N	0.592	0.616	None	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	8.89E-06	1.66334E-04
N/S	rs368106359	-0.945	0.999	N	0.592	0.616	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
N/S	rs368106359	-0.945	0.999	N	0.592	0.616	None	gnomAD-4.0.0	8.05777E-06	None	None	None	None	I	None	0	1.66722E-05	None	0	0	None	0	0	1.01734E-05	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	0.9675	likely_pathogenic	0.9659	pathogenic	-0.788	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
N/C	0.9241	likely_pathogenic	0.9276	pathogenic	-0.086	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
N/D	0.9114	likely_pathogenic	0.924	pathogenic	-1.065	Destabilizing	0.999	D	0.629	neutral	D	0.558513153	None	None	I
N/E	0.9955	likely_pathogenic	0.9953	pathogenic	-0.982	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	I
N/F	0.9985	likely_pathogenic	0.9986	pathogenic	-0.644	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
N/G	0.8961	likely_pathogenic	0.9021	pathogenic	-1.106	Destabilizing	1.0	D	0.569	neutral	None	None	None	None	I
N/H	0.9052	likely_pathogenic	0.9058	pathogenic	-0.952	Destabilizing	1.0	D	0.737	prob.delet.	D	0.5597806	None	None	I
N/I	0.9874	likely_pathogenic	0.9874	pathogenic	0.011	Stabilizing	1.0	D	0.707	prob.neutral	D	0.56003409	None	None	I
N/K	0.9959	likely_pathogenic	0.9958	pathogenic	-0.32	Destabilizing	1.0	D	0.733	prob.delet.	D	0.559273621	None	None	I
N/L	0.9742	likely_pathogenic	0.9748	pathogenic	0.011	Stabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
N/M	0.9887	likely_pathogenic	0.9889	pathogenic	0.539	Stabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	I
N/P	0.99	likely_pathogenic	0.9889	pathogenic	-0.226	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
N/Q	0.9935	likely_pathogenic	0.9929	pathogenic	-1.052	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	I
N/R	0.9917	likely_pathogenic	0.9913	pathogenic	-0.295	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	I
N/S	0.3379	likely_benign	0.3306	benign	-0.906	Destabilizing	0.999	D	0.592	neutral	N	0.499071826	None	None	I
N/T	0.7963	likely_pathogenic	0.7951	pathogenic	-0.649	Destabilizing	1.0	D	0.709	prob.delet.	D	0.522722716	None	None	I
N/V	0.9745	likely_pathogenic	0.9741	pathogenic	-0.226	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	I
N/W	0.9993	likely_pathogenic	0.9994	pathogenic	-0.432	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
N/Y	0.9857	likely_pathogenic	0.9867	pathogenic	-0.192	Destabilizing	1.0	D	0.725	prob.delet.	D	0.5597806	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.